02295nas a2200217 4500008004100000022001400041245016700055210006900222260007600291300001200367490000700379520140400386653002001790653002501810653003001835653003101865100001301896700002101909700001901930856012801949 2005 eng d a1087-057100aDevelopment of a simple assay protocol for high-throughput screening of mycobacterium tuberculosis glutamine synthetase for the identification of novel inhibitors0 aDevelopment of a simple assay protocol for highthroughput screen a2455 TELLER RD, THOUSAND OAKS, CA 91320 USAbSAGE PUBLICATIONS INCcOCT a725-7290 v103 a

Mycobacterium tuberculosis glutamine synthetase (GS) is an essential enzyme involved in the pathogenicity of the organism. The screening of a compound library using a robust high-throughput screening (HTS) assay is currently thought to be the most efficient way of getting lead molecules, which are potent inhibitors for this enzyme. The authors have purified the enzyme to a > 90% level from the recombinant Escherichia coli strain YMC21E, and it was used for partial characterization as well as standardization experiments. The results indicated that the K-m of the enzyme for L-glutamine and hydroxylamine were 60 mM and 8.3 mM, respectively. The K-m for ADP, arsenate, and Mn2+, were 2 mu M, 5 mu M, and 25 mu M, respectively. When the components were adjusted according to their K-m values, the activity remained constant for at least 3 h at both 25 degrees C and 37 degrees C. The Z' factor determined in microplate format indicated robustness of the assay. When the signal/noise ratios were determined for different assay volumes, it was observed that the 200-mu l volume was found to be optimum. The DMSO tolerance of the enzyme was checked up to 10%, with minimal inhibition. The IC50 value determined for L-methionine S-sulfoximine on the enzyme activity was 3 mM. Approximately 18,000 small molecules could be screened per day using this protocol by a Beckman Coulter HTS setup.

10aBeckman Coulter10aGlutamine synthetase10ahigh-throughput screening10aMycobacterium tuberculosis1 aSingh, U1 aPanchanadikar, V1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/development-simple-assay-protocol-high-throughput-screening-mycobacterium-tuberculosis-002437nas a2200217 4500008004100000022001400041245018800055210006900243260007600312300001400388490000700402520151700409653002001926653002601946653002501972653003001997653003102027100001902058700001902077856012302096 2006 eng d a1087-057100aDevelopment of a simple high-throughput screening protocol based on biosynthetic activity of Mycobacterium tuberculosis glutamine synthetase for the identification of novel inhibitors0 aDevelopment of a simple highthroughput screening protocol based  a2455 TELLER RD, THOUSAND OAKS, CA 91320 USAbSAGE PUBLICATIONS INCcDEC a1035-10420 v113 a

A high-throughput screening protocol has been developed for Mycobacterium tuberculosis glutamine synthetase by quantitative estimation of inorganic phosphate. The K., values determined at pH 6.8 are 22 mM for L-glutamic acid, 0.75 mM for NH4Cl, 3.25 mM for MgCl2, and 2.5 mM for adenosine triphosphate. The K-m value for glutamine is affected significantly by the increase in pH of assay buffer. At the saturating level of the substrate, the enzyme activity at pH 6.8 and 25 degrees C is found to be linear up to 3 h. The reduction of enzyme activity is negligible even in presence of 10% DMSO. The Z' factor and signal-to-noise ratio are found to be 0.75 and 6.18, respectively, when the enzyme is used at 62.5 mu g/ml concentration. The IC50 values obtained at pH 6.8 for both L-methionine S-sulfoximine and DL-phosphothriacin are 500 mu M and 30 pM, respectively, which is lowest compared to the values obtained at other pH levels. The Beckman Coulter high-throughput screening platform was found to take 5 h 9 min to complete the screening of 60 plates. For each assay plate, a replica plate is used to normalize the data. Screening of 1164 natural product fractions/extracts and synthetic molecules from an in-house library was able to identify 12 samples as confirmed hits. Altogether, the validation data from screening of a small set of an in-house library coupled with Z' and signal-to-noise values indicate that the protocol is robust for high-throughput screening of a diverse chemical library.

10aBeckman Coulter10abiosynthetic activity10aGlutamine synthetase10ahigh-throughput screening10aMycobacterium tuberculosis1 aSingh, Upasana1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/development-simple-high-throughput-screening-protocol-based-biosynthetic-activity-002207nas a2200265 4500008004100000245009000041210006900131260000800200300001200208490000700220520136600227100001701593700001901610700002501629700001901654700002001673700001901693700001601712700001801728700001801746700001801764700002001782700001901802856012001821 2006 eng d00aHigh-throughput screening of RNA polymerase inhibitors using a fluorescent UTP analog0 aHighthroughput screening of RNA polymerase inhibitors using a fl cDEC a968-9760 v113 a

RNA polymerase (RNAP) is a well-validated target for the development of antibacterial and antituberculosis agents. Because the purification of large quantities of native RNA polymerase from pathogenic mycobacteria is hazardous and cumbersome, the primary screening was carried out using Escherichia coli RNAP. The authors have developed a high-throughput screening (HTS) assay to screen for novel inhibitors of RNAP. In this assay, a fluorescent analog of UTP, gamma-amino naphthalene sulfonic acid (gamma-AmNS) UTP, was used as one of the nucleotide substrates. Incorporation of UMP in RNA results in the release of gamma-AmNS-PPi, which has higher intrinsic fluorescence than (gamma-AmNS) UTP. The assay was optimized in a 384-well format and used to screen 670,000 compounds at a concentration of 10 mu M. About 0.1% of the compounds showed more than 60% inhibition in the primary HTS. All the primary actives tested for dose response using the same assay had an EC50 below 100 mu M. Eighty percent of the primary HTS actives obtained using E. coli RNAP showed comparable activity against Mycobacterium smegmatis RNAP in the conventional radioactive assay. Activity of hits selected for the hit-to-lead optimization was also confirmed against Mycobacterium bovis RNAP which has > 99% sequence identity with Mycobacterium tuberculosis RNAP subunits.

1 aBhat, Jyothi1 aRane, Rajendra1 aSolapure, Suresh, M.1 aSarkar, Dhiman1 aSharma, Umender1 aHarish, M., N.1 aLamb, Sarah1 aPlant, Darren1 aAlcock, Peter1 aPeters, Steve1 aBarde, Shubhada1 aRoy, Raman, K. uhttps://library.ncl.res.in/content/high-throughput-screening-rna-polymerase-inhibitors-using-fluorescent-utp-analog02567nas a2200193 4500008004100000022001400041245012700055210006900182260008900251300001000340490000700350520178700357653002802144653002202172653001602194100001702210700001902227856012702246 2006 eng d a0882-401000aIdentification of a respiratory-type nitrate reductase and its role for survival of mycobacterium smegmatis in wayne model0 aIdentification of a respiratorytype nitrate reductase and its ro a24-28 OVAL RD, LONDON NW1 7DX, ENGLANDbACADEMIC PRESS LTD ELSEVIER SCIENCE LTDcAUG a90-950 v413 a

Nitrate reductase (NR) is found to be expressed in certain mycobacterium sp. whose link with the development of persistence is yet to be resolved. The present study demonstrates the action of selective inhibitors on NR as well as in the survival of Mycobacterium smegmatis using Wayne's model. During gradual shift down to anaerobic stage in Wayne's model, conversion of nitrate to nitrite became apparent in M. smegmatis. More than 97 percent inhibition was observed for the conversion of nitrate to nitrite by azide (0.05 mM) and thiocyanate (20 mM) in both whole-cell as well as its cell-free lysate, respectively. Under identical condition, chlorate (20 mM) inhibited nitrate reduction by 67 and 10 percent, respectively. At these concentrations, neither of azide, thiocyanate nor chlorate had any significant effect on cell growth under aerobic condition. In Wayne's culture model, thiocyanate and chlorate inhibited the growth of M. smegmatis by almost 2 logs at the same concentrations whereas azide inhibited by almost 1.75 log when added at the time of inoculation. Exposure of same culture at 96 h after inoculation in Wayne's model to these inhibitors showed 1.74, 1.95 and 2.37 log inhibition of viable cells with respect to azide, thiocyanate and chlorate. These findings further indicated that NR inhibitors kill the bacilli at anaerobic stage under the experimental condition mentioned. Metronidazole (MTZ) (2 mM) and Nitrofurantoin (NIT) (0.3 mM) reduced the cell number at both stages by < 0.7log. They did not have any effect on NR. Altogether, the results clearly indicate that NR-specific inhibitors could become more promising in killing the bacilli at anaerobic stage than the available conventional drugs. (c) 2006 Elsevier Ltd. All rights reserved.

10aMycobacterium smegmatis10anitrate reductase10aWayne model1 aKhan, Arshad1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/identification-respiratory-type-nitrate-reductase-and-its-role-survival-mycobacterium-002578nas a2200229 4500008004100000022001400041245019000055210006900245260007300314300001000387490000700397520165500404653002102059653002902080653002002109653002102129653001702150100001702167700001802184700001902202856012702221 2008 eng d a0924-857900aBactericidal activity of 2-nitroimidazole against the active replicating stage of mycobacterium bovis BCG and mycobacterium tuberculosis with intracellular efficacy in THP-1 macrophages0 aBactericidal activity of 2nitroimidazole against the active repl aPO BOX 211, 1000 AE AMSTERDAM, NETHERLANDSbELSEVIER SCIENCE BVcJUL a40-450 v323 a

This study evaluated the antituberculous potential of 2-nitroimidazole under in vitro conditions. Minimal bactericidal concentrations of the compound against actively replicating Mycobacterium bovis BCG and Mycobacterium tuberculosis H37Ra were found to be 0.226 mu g/mL and 0.556 mu g/mL in enriched and minimal medium, respectively. Minimal inhibitory concentrations were > 100 times lower than reported antituberculous nitroimidazoles such as nitrofurantoin and furaltadone, indicating the greater potential of 2-nitroimidazole. No discernible effect of 2-nitroimidazole was seen on saprophytic Mycobacterium smegmatis and the representative bacterial strain Escherichia coli DH5 alpha, indicating the specificity of the molecule against tuberculous mycobacteria. The compound was also found to be effective against M. tuberculosis in the intracellular environment of the human monocytic cell line THP-1, with a reduction in viability of bacilli by 2.5 log after 144 h of incubation at a concentration of 0.113 mu g/mL. A five-fold higher concentration (0.565 mu g/mL) of 2-nitroimidazole sterilised the macrophages of intracellular pathogens within 192 h, without affecting the host. However, 2-nitroimidazole was unable to affect significantly the viability of dormant non-replicating bacilli of M. bovis BCG and M. tuberculosis in Wayne's in vitro model. Overall, the results indicate that 2-nitroimidazole is a potent antituberculous agent active against the organism's active replicating stage, with promising intracellular efficacy as well. (c) 2008 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

10a2-nitroimidazole10aantimycobacterial agents10anitroimidazoles10aTHP-1 macrophage10atuberculosis1 aKhan, Arshad1 aSarkar, Sampa1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/bactericidal-activity-2-nitroimidazole-against-active-replicating-stage-mycobacterium-002448nas a2200241 4500008004100000022001400041245008500055210006900140260008900209300001000298490000700308520157200315653002001887653002501907653003101932653002801963653002501991100001702016700001902033700002102052700001902073856011402092 2008 eng d a0882-401000aPresence of a functional nitrate assimilation pathway in mycobacterium smegmatis0 aPresence of a functional nitrate assimilation pathway in mycobac a24-28 OVAL RD, LONDON NW1 7DX, ENGLANDbACADEMIC PRESS LTD ELSEVIER SCIENCE LTDcJAN a71-770 v443 a

Ability of Mycobacterium smegmatis to assimilate nitrate was evaluated in its active and dormant phase. Nitrate (10 mM), nitrite (0.5 mM) and ammonia (10 mM)allowed growth of M. smegmatis concomitant with their complete depletion from the culture in 144, 120 and 96 h, respectively, when used as sole nitrogen Source. Azide (50 mu M) stopped the growth of M. smegmatis when nitrate was used as sole nitrogen source. L-methionine-S-sulfoximine (L-MSO), which is a well-known inhibitor of glutamine synthetase, an enzyme also involved in nitrogen metabolic pathway, when applied at 10 mu g/ml concentration, completely inhibited the growth of the organism when nitrate or nitrite was used as sole nitrogen source. There was no effect of either azide or L-MSO at above concentrations on the growth of the organism when asparagine or ammonia was used as sole nitrogen source. More significantly, utilization of nitrate, nitrite and ammonia continued even in oxygen depletion induced dormant culture at the rates of 289, 25 and 354 mu M/day, respectively. These rates were 5-8 times slower than the rates of 1966, 127 and 2890 mu M/day, respectively, in active replicating phase. In the presence of azide (50 mu M) and L-MSO (10 mu g/ml), 2.1 and 1.51 logs reduction in viability of dormant M. smegmatis was observed using nitrate and nitrite, respectively, as sole nitrogen source. Altogether, the results indicated the presence of nitrate assimilation pathway operating in both active and dormant stage of M. smegmatis. (C) 2007 Elsevier Ltd. All rights reserved.

10aDormant bacilli10aGlutamine synthetase10aL-methionine-S-sulfoximine10aMycobacterium smegmatis10aNitrate assimilation1 aKhan, Arshad1 aAkhtar, Shamim1 aAhmad, Jawid, N.1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/presence-functional-nitrate-assimilation-pathway-mycobacterium-smegmatis-002115nas a2200205 4500008004100000022001400041245015200055210006900207260007300276300001000349490000700359520127600366653003001642653001701672653002701689653002701716100001701743700001901760856013001779 2008 eng d a0167-701200aSimple whole cell based high throughput screening protocol using Mycobacterium bovis BCG for inhibitors against dormant and active tubercle bacilli0 aSimple whole cell based high throughput screening protocol using aPO BOX 211, 1000 AE AMSTERDAM, NETHERLANDSbELSEVIER SCIENCE BVcAPR a62-680 v733 a

This study aimed at developing a whole cell based high throughput screening protocol to identify inhibitors against both active and dormant tubercle bacilli. A respiratory type of nitrate reductase (NarGHJI), which was induced during dormancy, could reflect the viability of dormant bacilli of Mycobacterium bovis BCG in microplate adopted model of in vitro dormancy. Correlation between reduction in viability and nitrate reductase activity was seen clearly when dormant stage inhibitor metronidazole and itaconic anhydride were applied in this in vitro microplate model. Active replicating stage could also be monitored in the same assay by measuring the A(620) of the culture. MIC values of 0.08, 0.075, 0.3 and 3.0 mu g/ml, determined through monitoring A(620) in this assay for rifampin, isoniazid, streptomycin and ethambutol respectively, were well in agreement with previously reported by BACTEC and Bio-Siv assays. S/N ratio and Z' factor for the assay were 8.5 and 0.81 respectively which indicated the robustness of the protocol. Altogether the assay provides an easy, inexpensive, rapid, robust and high content screening too] to search novel antitubercular molecules against both active and dormant bacilli. (C) 2008 Elsevier B.V. All rights reserved.

10ahigh throughput screening10atuberculosis10aWayne's dormancy model10awhole cell based assay1 aKhan, Arshad1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/simple-whole-cell-based-high-throughput-screening-protocol-using-mycobacterium-bovis-bcg-001689nas a2200277 4500008004100000022001400041245016700055210006900222260014100291300001400432490000700446520061700453653001501070653002101085653002001106653001001126653001801136100001801154700001301172700001501185700001901200700002101219700001701240700002601257856012801283 2009 eng d a1017-782500aProduction, purification, and characterization of taxol and 10-DABIII from a new endophytic fungus gliocladium sp isolated from the Indian yew tree, taxus baccata0 aProduction purification and characterization of taxol and 10DABI aKOREA SCI TECHNOL CENTER \#507, 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREAbKOREAN SOC MICROBIOLOGY & BIOTECHNOLOGYcNOV a1342-13470 v193 a

We have isolated endophytic fungi from the Indian yew tree, Taxus baccata, and then screened for taxol production. Out of the 40 fungal cultures screened, one fungus Gliocladium sp. was found to produce taxol and 10-DABIII (10-deacetyl baccatin III). These compounds were purified by TLC and HPLC and characterized using UV-spectroscopy, ESI-MS, MS/MS, and proton NMR. One liter of Gliocladium sp. culture yielded 10 mu g of taxol and 65 mu g of 10-DABIII. The purified taxol from the fungus showed cytotoxicity towards cancer lines HL-60 (leukemia), A431 (epidermal carcinoma), and MCF-7 (breast cancer).

10a10 DAB III10aEndophytic fungi10aGliocladium sp.10aTaxol10aTaxus baccata1 aSreekanth, D.1 aSyed, A.1 aSarkar, S.1 aSarkar, Dhiman1 aSanthakumari, B.1 aAhmad, Absar1 aKhan, Mohammad, Islam uhttps://library.ncl.res.in/content/production-purification-and-characterization-taxol-and-10-dabiii-new-endophytic-fungus-001275nas a2200253 4500008004100000022001400041245006000055210006000115260009500175300001200270490000800282520047900290653001200769653001200781653001700793653001800810653001600828653001100844100001900855700001800874700002100892700001900913856008900932 2011 eng d a0003-269700aMethod to extract intact and pure RNA from mycobacteria0 aMethod to extract intact and pure RNA from mycobacteria a525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USAbACADEMIC PRESS INC ELSEVIER SCIENCEcOCT a286-2880 v4173 a

We describe a high-yielding, simple, and aerosol-free protocol for the isolation of RNA from mycobacteria that does not require sophisticated instruments. The method yielded 50 mu g of RNA from 10(7) cells, 50 times more than a recently reported method. Our method can extract total RNA from aerobically grown bacteria and from in vitro hypoxia-induced dormant bacilli and mycobacteria residing within infected macrophages. (C) 2011 Elsevier Inc. All rights reserved.

10aDormant10aHypoxia10aMycobacteria10aRNA isolation10aSpheroplast10aTrizol1 aAkhtar, Shamim1 aSarkar, Sampa1 aMishra, Abhishek1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/method-extract-intact-and-pure-rna-mycobacteria-002740nas a2200229 4500008004100000022001400041245013200055210006900187260007300256300001200329490000700341520187900348653001402227653003102241653002102272653000902293100001902302700001902321700002102340700001902361856013002380 2011 eng d a0167-701200aNovel screening method based on menadione mediated rapid reduction of tetrazolium salt for testing of anti-mycobacterial agents0 aNovel screening method based on menadione mediated rapid reducti aPO BOX 211, 1000 AE AMSTERDAM, NETHERLANDSbELSEVIER SCIENCE BVcFEB a202-2070 v843 a

A microplate-based rapid, inexpensive and robust technique is developed by using tetrazolium salt 2, 3-bis [2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) and menadione to determine the viability of Mycobacterium tuberculosis, Mycobacterium bovis BCG and Mycobacterium smegmatis bacilli in microplate format. In general, XTT reduction is an extremely slow process which takes almost 24 h to produce a detectable signal. Menadione could drastically induce this reduction to an almost equal extent within a few minutes in a dose dependent manner. The reduction of XTT is directly proportional to the cell concentration in the presence of menadione. The standardized protocol used 200 mu M of XTT and 60 mu M of menadione in 250 mu l of cell suspension grown either in aerobic or anaerobic conditions. The cell suspension of M. bovis BCG and M. tuberculosis were incubated for 40 min before reading the optical density at 470 nm whereas M. smegmatis was incubated for 20 min. Calculated Signal/Noise (S/N) ratios obtained by applying this protocol were 5.4, 6.4 and 9.4 using M. bovis BCG. M. tuberculosis and M. smegmatis respectively. The calculated Z' factors were > 0.8 for all mycobacterium bacilli indicating the robustness of the XTT Reduction Menadione Assay (XRMA) for rapid screening of inhibitors. The assay protocol was validated by applying 10 standard anti-tubercular agents on M. tuberculosis, M. bovis BCG and M. smegmatis. The Minimum Inhibitory Concentration (MIC) values were found to be similar to reported values from Colony Forming Unit (CFU) and REMA (resazurin microplate assay) assays. Altogether. XRMA is providing a novel anti-tubercular screening protocol which could be useful in high throughput screening programs against different physiological stages of the bacilli. (C) 2010 Elsevier B.V. All rights reserved.

10aMenadione10aMycobacterium tuberculosis10aTetrazolium salt10aXRMA1 aSingh, Upasana1 aAkhtar, Shamim1 aMishra, Abhishek1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/novel-screening-method-based-menadione-mediated-rapid-reduction-tetrazolium-salt-testing-001896nas a2200157 4500008004100000022001400041245008500055210006900140260011800209300001200327490000800339520123600347100001701583700001901600856011901619 2012 eng d a1350-087200aNitrate reduction pathways in mycobacteria and their implications during latency0 aNitrate reduction pathways in mycobacteria and their implication aMARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLANDbSOC GENERAL MICROBIOLOGYcFEB a301-3070 v1583 a

Mycobacterial persistence has gained a lot of attention with respect to developing novel antitubercular drugs, which could drastically reduce the duration of tuberculosis (TB) therapy. A better understanding of the physiology of Mycobacterium tuberculosis, and of the metabolic state of the bacillus during the latent period, is a primary need in finding drug targets against persistent TB. Recent biochemical and genetic studies of nitrate reduction in mycobacteria have revealed the roles of distinct proteins and enzymes involved in the pathway. The differential degree of nitrate reduction among pathogenic and non-pathogenic mycobacterial species, and its regulation during oxygen and nutrient limitation, suggest a link between nitrate reduction pathways and latency. The respiratory and assimilatory reduction of nitrate in mycobacteria may be interconnected to facilitate rapid adaptation to changing oxygen and/or nitrogen conditions, increasing metabolic flexibility for survival in the hostile host environment. This review summarizes the nitrate metabolic pathways operative in mycobacteria to provide an insight into the mechanisms that M. tuberculosis has evolved to adapt successfully to the host environment.

1 aKhan, Arshad1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/nitrate-reduction-pathways-mycobacteria-and-their-implications-during-latency-001774nas a2200253 4500008004100000022001400041245005400055210005400109260009200163300001400255490000700269520092500276653002401201653001401225653003101239653002901270100002501299700002101324700002301345700001901368700002601387700002101413856008601434 2012 eng d a1028-602000aPhyllocladane diterpenes from anisomeles heyneana0 aPhyllocladane diterpenes from anisomeles heyneana a4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLANDbTAYLOR & FRANCIS LTDcNOV a1162-11680 v143 a

New phyllocladane diterpene, phyllocladan-16 alpha,17-dihydroxy-19-oic acid (1), together with known phyllocladane diterpene, phyllocladan-16 alpha,19-diol (2), cembrane diterpene ovatodiolide (3), sitosteryl-3-O-beta-D-glucoside (4), and verbascoside (5), were isolated from aerial parts of Anisomeles heyneana. The structure of compound 1 was elucidated by 1D and 2D NMR analyses which included HSQC, HMBC, and nuclear overhauser effect spectroscopy (NOESY) experiments as well as X-ray crystallography. This is the first report of phyllocladane diterpenes from genus Anisomeles. Compounds 1, 3, 4, and 5 were evaluated for inhibition of Mycobacterium tuberculosis and 3 was found to exhibit anti-mycobacterial activity with IC90 6.53 mu g/ml. Compounds 1, 3, and 5, at 100 mu g/ml, were also evaluated for inhibition of Thp-1 cell lines, and compounds 1 and 3 showed 59.02% and 96.4% inhibitions, respectively.

10aAnisomeles heyneana10aLamiaceae10aMycobacterium tuberculosis10aphyllocladane diterpenes1 aKulkarni, Roshan, R.1 aShurpali, Ketaki1 aGawade, Rupesh, L.1 aSarkar, Dhiman1 aPuranik, Vedavati, G.1 aJoshi, Swati, P. uhttps://library.ncl.res.in/content/phyllocladane-diterpenes-anisomeles-heyneana-002223nas a2200217 4500008004100000022001400041245016600055210006900221260007600290300001200366490000700378520134900385653003001734653001401764653003101778653002201809653000901831100001801840700001901858856012801877 2012 eng d a1087-057100aPotential use of nitrate reductase as a biomarker for the identification of active and dormant inhibitors of mycobacterium tuberculosis in a THP1 infection model0 aPotential use of nitrate reductase as a biomarker for the identi a2455 TELLER RD, THOUSAND OAKS, CA 91320 USAbSAGE PUBLICATIONS INCcAUG a966-9730 v173 a

The development of a macrophage-based, antitubercular high-throughput screening system could expedite discovery programs for identifying novel inhibitors. In this study, the kinetics of nitrate reduction (NR) by Mycobacterium tuberculosis during growth in Thp1 macrophages was found to be almost parallel to viable bacilli count. NR in the culture medium containing 50 mM of nitrate was found to be optimum on the fifth day after infection with M. tuberculosis. The signal-to-noise (S/N) ratio and Z-factor obtained from this macrophage-based assay were 5.4 and 0.965, respectively, which confirms the robustness of the assay protocol. The protocol was further validated by using standard antitubercular inhibitors such as rifampicin, isoniazid, streptomycin, ethambutol, and pyrazinamide, added at their IC90 value, on the day of infection. These inhibitors were not able to kill the bacilli when added to the culture on the fifth day after infection. Interestingly, pentachlorophenol and rifampicin killed the bacilli immediately after addition on the fifth day of infection. Altogether, this assay protocol using M. tuberculosis-infected Thp-1 macrophages provides a novel, cost-efficient, robust, and easy-to-perform screening platform for the identification of both active and hypoxic stage-specific inhibitors against tuberculosis.

10ahigh-throughput screening10ainhibitor10aMycobacterium tuberculosis10anitrate reductase10aTHP11 aSarkar, Sampa1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/potential-use-nitrate-reductase-biomarker-identification-active-and-dormant-inhibitors-003028nas a2200169 4500008004100000245016800041210007100209260000800280520230800288100002502596700001802621700001902639700002102658700002802679700001802707856013302725 2012 eng d00aSelf–assembled histidine acid phosphate nanocapsules as templates for multifunctional hollow platinum nanospheres in ionic liquid [BMIM][BF 4 ] for drug delivery0 aSelf–assembled histidine acid phosphate nanocapsules as template cJAN3 a

During the past few decades, the design and fabrication of nano drug delivery vehicle has received considerable attention for incorporating multi-functionality, emphasizing transportation of anticancer drugs to tumour sites. Protein-based nanoparticles hold significant promise in the development of anticancer drug delivery systems since they have remarkable superiority in biocompatibility, biodegradability and natural metabolism in physiologic systems. Ionic liquids (ILs) are a class of solvents that are composed solely of ions (ILs – commonly referred as room temperature molten salts or room temperature ionic liquids). They have recently emerged as green solvents or green reaction media, because of their reported unique physico-chemical properties. We report for the first time the controlled self-assembly of Histidine Acid phosphatase (HAP) enzyme in the IL 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM][BF 4 ], leading to the formation of HAP nanocapsules as template for synthesis of platinum nanospheres. These HAP nano-containers were loaded with an anticancer drug curcumin. We further demonstrated in vitro drug release and synergistic anticancer effect of these systems on three different cell lines viz. hepatocellular carcinoma (HepG2), breast cancer (MCF-7) and human acute monocytes (THP-1). The present work can extend our theoretical understanding on nano-bio interfacial molecular self assembly and will facilitate the motivated insights of inorganic/organic hybrid nano-materials/ nano-particles/ nano-objects and ionic liquids based multi functional drug delivery vehicles with synergistic combination chemotherapy for potential application in tumor targeting. INTRODUCTION During the past few decades, the design and fabrication of drug delivery vehicle has received considerable attention for incorporating multi-functionality emphasizing transportation of anticancer drugs to tumour sites. These nano drug delivery vehicles have many advantages including prolonged circulation time of the drugs (Duncan, 2003, Kiick, 2007) , improved drug targeting and solubility (Duncan, 2003, Kiick, 2007), higher payloads (Duncan, 2003) and controlled release of the therapeutics into the blood stream or the targeted tumour tissues (Uhrich et al. 1999, Duncan, 2003).

1 aSoni, Sarvesh, Kumar1 aSarkar, Sampa1 aSarkar, Dhiman1 aColoe, Peter, J.1 aBhargava, Suresh, Kumar1 aBansal, Vipul uhttps://library.ncl.res.in/content/self%E2%80%93assembled-histidine-acid-phosphate-nanocapsules-templates-multifunctional-hollow01219nas a2200193 4500008004100000022001400041245006400055210006400119260007100183300001400254490000700268520054200275100002500817700002100842700002600863700001900889700002100908856009600929 2013 eng d a0163-386400aAntimycobacterial labdane diterpenes from leucas stelligera0 aAntimycobacterial labdane diterpenes from leucas stelligera a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcOCT a1836-18410 v763 a

Phytochemical investigation of the acetone extract of the aerial parts of Leucas stelligera afforded four new compounds (1-4) belonging to the labdane diterpene series as well as two known flavones, velutin (5) and chrysoeriol (6). Structure elucidation of the new compounds was carried out using ID and 2D NMR spectroscopic data and single-crystal X-ray crystallography of compound 1. Compounds 1-4 exhibited selective antimycobacterial activity against Mycobacterium tuberculosis with IC50 values in the range 5.02-9.80 mu g/mL.

1 aKulkarni, Roshan, R.1 aShurpali, Ketaki1 aPuranik, Vedavati, G.1 aSarkar, Dhiman1 aJoshi, Swati, P. uhttps://library.ncl.res.in/content/antimycobacterial-labdane-diterpenes-leucas-stelligera-002422nas a2200193 4500008004100000022001400041245012200055210006900177260007600246300001400322490000800336520165600344100001902000700001702019700002602036700002702062700001902089856012002108 2013 eng d a0021-919300aNitrite reductase NirBD is induced and plays an important role during in vitro dormancy of mycobacterium tuberculosis0 aNitrite reductase NirBD is induced and plays an important role d a1752 N ST NW, WASHINGTON, DC 20036-2904 USAbAMER SOC MICROBIOLOGYcOCT a4592-45990 v1953 a

Mycobacterium tuberculosis is one of the strongest reducers of nitrate among all mycobacteria. Reduction of nitrate to nitrite, mediated by nitrate reductase (NarGHJI) of M. tuberculosis, is induced during the dormant stage, and the enzyme has a respiratory function in the absence of oxygen. Nitrite reductase (NirBD) is also functional during aerobic growth when nitrite is the sole nitrogen source. However, the role of NirBD-mediated nitrite reduction during the dormancy is not yet characterized. Here, we analyzed nitrite reduction during aerobic growth as well as in a hypoxic dormancy model of M. tuberculosis in vitro. When nitrite was used as the sole nitrogen source in the medium, the organism grew and the reduction of nitrite was evident in both hypoxic and aerobic cultures of M. tuberculosis. Remarkably, the hypoxic culture of M. tuberculosis, compared to the aerobic culture, showed 32- and 4-fold-increased expression of nitrite reductase (NirBD) at the transcription and protein levels, respectively. More importantly, a nirBD mutant of M. tuberculosis was unable to reduce nitrite and compared to the wild-type (WT) strain had a >2-log reduction in viability after 240 h in the Wayne model of hypoxic dormancy. Dependence of M. tuberculosis on nitrite reductase (NirBD) was also seen in a human macrophage-based dormancy model where the nirBD mutant was impaired for survival compared to the WT strain. Overall, the increased expression and essentiality of nitrite reductase in the in vitro dormancy models suggested that NirBD-mediated nitrite reduction could be critical during the persistent stage of M. tuberculosis.

1 aAkhtar, Shamim1 aKhan, Arshad1 aSohaskey, Charles, D.1 aJagannath, Chinnaswamy1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/nitrite-reductase-nirbd-induced-and-plays-important-role-during-vitro-dormancy-001725nas a2200277 4500008004100000022001400041245013000055210006900185260010600254300001200360490000700372520065700379653002201036653002801058653002701086653002201113100002201135700002601157700001901183700002901202700002401231700002301255700002401278700001901302856012601321 2013 eng d a0960-894X00aOne pot solvent free synthesis and in vitro antitubercular screening of 3-aracylphthalides against mycobacterium tuberculosis0 aOne pot solvent free synthesis and in vitro antitubercular scree aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcFEB a711-7140 v233 a

One pot synthesis of 3-Aracylphthalide was accomplished in good yield by reacting 2-carboxy benzaldehyde with various aromatic methyl ketones in presence of methane sulphonic acid. Various phthalides thus obtained were characterized with spectral techniques. These phthalides were subjected to in vitro antitubercular screening against Mycobacterium tuberculosis H37Ra (MTB) by using XRMA protocol. Among the phthalides screened, four exhibited half maximal inhibitory concentration (IC50) in the range of 0.81-1.24 mu g/ml thereby providing potential lead compounds for future drug discovery studies. (c) 2012 Elsevier Ltd. All rights reserved.

10a3-Aracylphthalide10aAntitubercular activity10aMethane sulphonic acid10aOne pot synthesis1 aLimaye, Rohan, A.1 aKumbhar, Virendra, B.1 aNatu, Arun, D.1 aParadkar, Madhusudan, V.1 aHonmore, Varsha, S.1 aChauhan, Rubia, R.1 aGample, Suvarna, P.1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/one-pot-solvent-free-synthesis-and-vitro-antitubercular-screening-3-aracylphthalides-000813nas a2200205 4500008004100000022001400041245011200055210006900167260007300236300000800309490000800317100002800325700001900353700003100372700002100403700002100424700002100445700001900466856012200485 2014 eng d a0168-165600aAdvanced cell-based high-throughput screening assays targeting active and latent Mycobacterium tuberculosis0 aAdvanced cellbased highthroughput screening assays targeting act aPO BOX 211, 1000 AE AMSTERDAM, NETHERLANDSbELSEVIER SCIENCE BVcSEP aS180 v1851 aShurpali, Ketaki, Dilip1 aSingh, Upasana1 aSarkar, Shamim, Akhtar Sam1 aMishra, Abhishek1 aKulkarni, Roshan1 aJoshi, Swati, P.1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/advanced-cell-based-high-throughput-screening-assays-targeting-active-and-latent-001991nas a2200289 4500008004100000022001400041245008900055210006900144260009200213300001200305490000700317520096500324653002501289653001501314653002101329653002101350653002801371653001401399100002501413700002201438700002401460700003001484700001901514700002601533700002101559856012101580 2014 eng d a1478-641900aAntifungal dimeric chalcone derivative kamalachalcone E from Mallotus philippinensis0 aAntifungal dimeric chalcone derivative kamalachalcone E from Mal a4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLANDbTAYLOR & FRANCIS LTDcFEB a245-2500 v283 a

From the red coloured extract (Kamala) prepared through acetone extraction of the fresh whole uncrushed fruits of Mallotus philippinensis, one new dimeric chalcone (1) along with three known compounds 1-(5,7-dihydroxy-2,2,6-trimethyl-2H-1-benzopyran-8-yl)-3-phenyl-2-propen -1-one (2), rottlerin (3) and 4 `-hydroxyrottlerin (4) were isolated. The structure of compound 1 was elucidated by 1D and 2D NMR analyses that included HSQC, HMBC, COSY and ROESY experiments along with the literature comparison. Compounds 1-4 were evaluated for antifungal activity against different human pathogenic yeasts and filamentous fungi. The antiproliferative activity of the compounds was evaluated against Thp-1 cell lines. Compounds 1 and 2 both exhibited IC50 of 8, 4 and 16 mu g/mL against Cryptococcus neoformans PRL518, C. neoformans ATCC32045 and Aspergillus fumigatus, respectively. Compound 4, at 100 mu g/mL, showed 54% growth inhibition of Thp-1 cell lines.

10a4 `-hydroxyrottlerin10aantifungal10adimeric chalcone10akamalachalcone E10aMallotus philippinensis10arottlerin1 aKulkarni, Roshan, R.1 aTupe, Santosh, G.1 aGample, Suvarna, P.1 aChandgude, Macchindra, G.1 aSarkar, Dhiman1 aDeshpande, Mukund, V.1 aJoshi, Swati, P. uhttps://library.ncl.res.in/content/antifungal-dimeric-chalcone-derivative-kamalachalcone-e-mallotus-philippinensis-001843nas a2200181 4500008004100000245010200041210006900143260000800212520117100220100001801391700002501409700002101434700002301455700002001478700001801498700001901516856012601535 2014 eng d00aAptamer functionalized multifunctional fluorescent nanotheranostic platform for pancreatic cancer0 aAptamer functionalized multifunctional fluorescent nanotheranost cDEC3 aThis study explores the potential of aptamer functionalized and fluorescent silver nanoparticles (AgNPs) labeled human serum albumin nanoparticles for drug delivery and bioimaging. Nanotechnology is certainly the most promising research arena in recent years and different fields of biotechnology, medicine and agricultural have been deeply benefited by the enormous advantages of nanotechnology. In recent years, synthesis of nanoparticles via eco-friendly methods has attained a lot of interest and silver nanoparticles are synthesized extensively due to their size tunable properties and vast applicability in different areas. In this study we have explored green synthesized fluorescent silver nanoparticles as a novel bioimaging agent for pancreatic cancer. Capsaicin, a plant phytochemical found in red chilli pepper was encapsulated in aptamer MUC-1 coupled albumin nanoparticles and it was observed that the nanoformulation significantly enhanced the bioavailability and sustained release property of the drug to pancreatic cancer cells in-vitro. Meanwhile AgNPs mediated excellent bioimaging has enhanced the efficacy of our system as drug delivery vehicle.1 aNigam, Preeti1 aWaghmode, Shobha, A.1 aYeware, Amar, M.1 aNawale, Laxman, U.1 aDagde, Priyanka1 aDudhane, Amol1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/aptamer-functionalized-multifunctional-fluorescent-nanotheranostic-platform-pancreatic02008nas a2200205 4500008004100000022001400041245011900055210006900174260011000243300001400353490000600367520117900373100001801552700002101570700002001591700002301611700001801634700001901652856013101671 2014 eng d a2050-750X00aGraphene quantum dots conjugated albumin nanoparticles for targeted drug delivery and imaging of pancreatic cancer0 aGraphene quantum dots conjugated albumin nanoparticles for targe aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcJUN a3190-31950 v23 a

Pancreatic cancer is considered to be the deadliest of all cancers due to its poor prognosis and resistance to conventional therapies. In this study, the potential of hyaluronic acid functionalized and green fluorescent graphene quantum dot (GQD)-labeled human serum albumin nanoparticles for pancreatic cancer specific drug delivery and bioimaging was explored. GQDs with tunable fluorescence properties and biocompatibility have attracted much more interest in recent years as compared to their metal semiconductor counterparts. We adopted lawsone (2-hydroxy-1,4-naphthoquinone) as a novel reducing agent for the synthesis of quantum dots and, in addition to excellent fluorescence of the synthesized GQDs, a good quantum yield of similar to 14% was also obtained. Gemcitabine, the most preferred drug for pancreatic cancer treatment, was encapsulated in albumin nanoparticles, and it was observed that our nanoformulation significantly enhanced the bioavailability and sustained release property of the drug to pancreatic cancer cells in vitro. Moreover, the GQD-mediated bioimaging was excellent and enhanced the efficacy of our system as a drug delivery vehicle.

1 aNigam, Preeti1 aWaghmode, Shobha1 aLouis, Michelle1 aWangnoo, Shishanka1 aChavan, Pooja1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/graphene-quantum-dots-conjugated-albumin-nanoparticles-targeted-drug-delivery-and-imaging-001444nas a2200193 4500008004100000022001400041245026000055210006900315260011000384300001400494490000600508520048100514100003100995700002701026700002401053700002401077700001901101856013001120 2014 eng d a2046-206900aHighly efficient one-pot multi-component synthesis of alpha-aminophosphonates and bis-alpha-aminophosphonates catalyzed by heterogeneous reusable silica supported dodecatungstophosphoric acid (DTP/SiO2) at ambient temperature and their antitubercular eval0 aHighly efficient onepot multicomponent synthesis of alphaaminoph aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcJAN a7666-76720 v43 a

A highly efficient one-pot multi-component reaction (MCR) protocol over DTP/SiO2 has been developed for the synthesis of alpha-aminophosphonate derivatives (4a-x) in excellent yields. The alpha-aminophosphonate derivatives were for the first time evaluated for their antitubercular activity against the M. tuberculosis H37Ra (MTB) strain. An evaluation of the data on the cytotoxicity and antimicrobial activity shows that 4n and 4v are promising antitubercular agents.

1 aMulla, Shafeek, Abdul Rash1 aPathan, Mohsinkhan, Y.1 aChavan, Santosh, S.1 aGample, Suvarna, P.1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/highly-efficient-one-pot-multi-component-synthesis-alpha-aminophosphonates-and-bis-alpha-002287nas a2200217 4500008004100000022001400041245011800055210006900173260011000242300001400352490000600366520139800372100002401770700003001794700001901824700001901843700002601862700003101888700002601919856012401945 2015 eng d a2040-250300a1,2,3-Triazole derivatives as antitubercular agents: synthesis, biological evaluation and molecular docking study0 a123Triazole derivatives as antitubercular agents synthesis biolo aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcMAY a1104-11160 v63 a

Searching for new active molecules against Mycobacterium tuberculosis (MTB) H37Ra, a small focused library of 1,2,3-triazoles has been efficiently prepared via a click chemistry approach. The newly synthesized compounds were tested against drug-sensitive MTB. Several derivatives were found to be promising inhibitors of MTB characterized by lower MIC values (5.8-29.9 mu g mL(-1)). Among all the synthesized 31 compounds, 15e was the most active compound against MTB. Based on the results from the antitubercular activity, SAR for the synthesized series has been developed. The active compounds from the anti-tubercular study were further tested for anti-proliferative activity against THP-1, A549 and PANC-1 cell lines using MTT assay and showed no significant cytotoxic activity against these three cell lines except THP-1 at the maximum concentration evaluated. Further, the synthesized compounds were found to have potential antioxidant activities with an IC50 range of 10.1-37.3 mu g mL(-1). The molecular docking study of the synthesized compounds was performed against the DprE1 enzyme of MTB to understand the binding interactions. Moreover, the synthesized compounds were also analysed for ADME properties and all the experimental results promote us to consider this series as a starting point for the development of novel and more potent anti-tubercular agents in the future.

1 aShaikh, Mubarak, H.1 aSubhedar, Dnyaneshwar, D.1 aNawale, Laxman1 aSarkar, Dhiman1 aKhan, Firoz, A. Kalam1 aSangshetti, Jaiprakash, N.1 aShingate, Bapurao, B. uhttps://library.ncl.res.in/content/123-triazole-derivatives-antitubercular-agents-synthesis-biological-evaluation-and-001578nas a2200169 4500008004100000245011800041210006900159260000800228300000900236490000700245520095900252100001901211700001901230700001901249700001901268856012101287 2015 eng d00aAnalyzing different acetyl co-a metabolizing enzymes as potential drug targets against mycobacterium tuberculosis0 aAnalyzing different acetyl coa metabolizing enzymes as potential cSEP a1-150 v103 a

Mycobacterium tuberculosis, the causative agent of tuberculosis, is responsible for the deaths of million people around the globe. The scenario is worse than ever due to the emergence of drug resistant strains which are widely spread throughout the globe in much faster ways. To control this worst situation, we need to speed up the search for novel drugs which can specifically kill drug resistant bacteria in collaborative ways amongst academic, clinician and industry. Among different metabolic pathways, fatty acid synthesis pathway has always been a very attractive area for the drug target because of its crucial role during the infection and further in long term survival of pathogen inside the human host. In this review article, we analyzed the role of important and crucial enzymes, which are responsible for the influx and efflux of acetyl co-A substrate, a central hub of metabolites, as potential drug targets against M. tuberculosis.

1 aAkhtar, Shamim1 aSingh, Sheetal1 aKumar, Santosh1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/analyzing-different-acetyl-co-metabolizing-enzymes-potential-drug-targets-against01529nas a2200181 4500008004100000245009000041210006900131260000800200300001000208490000600218520089800224100002901122700002101151700002401172700001901196700002101215856011101236 2015 eng d00aAntimycobacterium activity of coumarins from fruit pulp of aegle marmelos (L.) correa0 aAntimycobacterium activity of coumarins from fruit pulp of aegle cJUL a39-440 v53 a

Phytochemical investigation of n-butanol fraction of acetone extract of Aegle marmelos fruit has afforded four compounds coumarins marmelosin (1), marmin (2) and xanthotoxol (3) and flavonoid kaempferol 3- O-rhamnoside, afzelin (4). All the isolated compounds were evaluated for their antimycobacterium activity against Mycobacterium tuberculosis H37Ra and Mycobacterium bovis. Compounds 1 and 2 exhibited antimycobacterium activity against M. tuberculosis H37Ra with an IC50 12.46 µg/mL and 4.31 µg/mL respectively whereas, at 100 µg/mL, 62.5% and 82.4% growth inhibition of M. bovis was observed respectively. Compounds 1 and 2 were also evaluated against two gram positive bacteria Staphylococcus aureus, Bacillus subtilis and one gram negative bacteria Escherichia coli. Compound 1 at 100 µg/mL, showed growth inhibition, 64.6% and 74.9% of E. coli and B. subtilis respectively.

1 aChinchansure, Ashish, A.1 aShamnani, Neelam1 aArkile, Manisha, A.1 aSarkar, Dhiman1 aJoshi, Swati, P. uhttps://library.ncl.res.in/content/antimycobacterium-activity-coumarins-fruit-pulp-aegle-marmelos-l-correa02356nas a2200289 4500008004100000022001400041245009700055210006900152260007300221300001200294490000700306520133900313653002601652653002801678653001701706653001701723653001801740653001701758100001701775700002301792700002401815700002901839700002501868700001901893700002601912856012801938 2015 eng d a0924-857900aChemical and biological metal nanoparticles as antimycobacterial agents: a comparative study0 aChemical and biological metal nanoparticles as antimycobacterial aPO BOX 211, 1000 AE AMSTERDAM, NETHERLANDSbELSEVIER SCIENCE BVcAUG a183-1880 v463 a

Resistance among mycobacteria leading to multidrug-resistant and extensively drug-resistant tuberculosis is a major threat. However, nanotechnology has provided new insights in drug delivery and medicine development. This is the first comparative report to determine the activity of chemically and biologically synthesised silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) against mycobacteria. Screening data revealed the high mycobactericidal efficiency of AgNPs, with minimum inhibitory concentrations (MICs) of <3 mu g/mL, whereas no such activity was exhibited by AuNPs at concentrations up to 100 mu g/mL. Moreover, in vitro and ex vivo THP-1 infection model assays showed greater efficacy of chemical AgNPs compared with biogenic AgNPs to inhibit active and dormant stage mycobacterial growth. Up to 40% cytotoxicity against human cell lines was observed at a AgNP concentration of 10 x MIC (30 mu g/mL) after 48 h. AgNPs were shown to have more specificity towards mycobacteria than towards other Gram-negative and Gram-positive pathogenic bacteria. The selectivity index was found to be in the range of 11-23, indicating the potential of these nanoparticles for use in developing new therapeutics for tuberculosis. (C) 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

10aAntibiotic resistance10aAntimycobacterial agent10aCytotoxicity10aMycobacteria10aNanoparticles10atuberculosis1 aSingh, Richa1 aNawale, Laxman, U.1 aArkile, Manisha, A.1 aShedbalkar, Utkarsha, U.1 aWadhwani, Sweety, A.1 aSarkar, Dhiman1 aChopade, Balu, Ananda uhttps://library.ncl.res.in/content/chemical-and-biological-metal-nanoparticles-antimycobacterial-agents-comparative-study-002486nas a2200265 4500008004100000022001400041245010900055210006900164260010600233300001400339490000700353520150900360653002101869653001501890653001801905653001801923653001901941100002201960700002401982700002902006700002302035700002302058700001902081856012002100 2015 eng d a0960-894X00aDesign and synthesis of 11 alpha-substituted bile acid derivatives as potential anti-tuberculosis agents0 aDesign and synthesis of 11 alphasubstituted bile acid derivative aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcOCT a4185-41900 v253 a

We have synthesized a series of novel 11 alpha-triazoyl bile acid derivatives. In addition, we also have synthesized N-alkyl and N-acyl derivatives of C-11 amino bile acid esters. All the compounds were evaluated for the inhibitory activity against Mycobacterium tuberculosis H37Ra (MTB) at 30 mu g/mL level. Four lead compounds (2b, 3, 7 and 8) were further confirmed from their dose dependent effect against MTB. These compounds were found to be active against Dormant and active stage MTB under both in vitro as well as within THP1 host macrophages. The most promising compound 2b showed strong antitubercular activities against MTB under in vitro and ex vivo (IC90 value of similar to 3 mu g/mL) conditions and almost insignificant cytotoxicity up to 100 mu g/mL against THP-1, A549 and PANC-1 human cancer cell lines. Inactivity of all these compounds against Gram positive and Gram negative bacteria indicates their specificity. Molecular docking studies of these compounds into the active site of DprE1 enzyme revealed a similar binding mode to native ligands in the crystal structure thereby helping to establish a structural basis of inhibition of MTB. The synthesized compounds were analyzed for ADME properties and showed potential to develop good oral drug candidates. Our results clearly indicate the identification of some novel, selective and specific inhibitors against MTB that can be explored further for potential antitubercular drug. (C) 2015 Elsevier Ltd. All rights reserved.

10aAntituberculosis10aBile acids10aCycloaddition10aDocking study10aIn silico ADME1 aPore, Vandana, S.1 aDivse, Jaisingh, M.1 aCharolkar, Chaitanya, R.1 aNawale, Laxman, U.1 aKhedkar, Vijay, M.1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/design-and-synthesis-11-alpha-substituted-bile-acid-derivatives-potential-anti-001879nas a2200325 4500008004100000022001400041245012300055210006900178260007100247300001400318490000600332520075200338653002101090653002801111653001701139653002301156653003101179653001601210653001201226100002401238700001801262700002401280700001601304700002101320700002401341700002601365700001901391700002301410856012001433 2015 eng d a1948-587500aDesign and synthesis of a focused library of diamino triazines as potential mycobacterium tuberculosis DHFR inhibitors0 aDesign and synthesis of a focused library of diamino triazines a a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcNOV a1140-11440 v63 a

We report design of a series of 2,4-diamino triazines as Mycobacterium tuberculosis (Mtb) dihydrofolate reductase inhibitors. The synthesized compounds were evaluated against Mtb (H(37)Rv and Dormant stage H37Ra), their cytotoxicity was assessed (HepG2 and A549 cell lines), and selectivity toward Mtb was evaluated by testing against other bacterial strains. Some derivatives showed promising activity along with low cytotoxicity. The most potent compound in the whole cell assay (MIC 0.325 mu M against H(37)Rv) showed selectivity in the enzyme assay and exhibited synergy with second line anti-TB agent p-amino salicylic acid. This study therefore provides promising molecules for further development as antituberculosis DHFR inhibitors.

10aDiamino triazine10adihydrofolate reductase10aenzyme assay10amolecular modeling10aMycobacterium tuberculosis10aselectivity10asynergy1 aLele, Arundhati, C.1 aRaju, Archana1 aKhambete, Mihir, P.1 aRay, M., K.1 aRajan, M., G. R.1 aArkile, Manisha, A.1 aJadhav, Nandadeep, J.1 aSarkar, Dhiman1 aDegani, Mariam, S. uhttps://library.ncl.res.in/content/design-and-synthesis-focused-library-diamino-triazines-potential-mycobacterium-000566nas a2200109 4500008004100000245009600041210006900137260009100206100001900297700001900316856012100335 2015 eng d00aDiscovery of new chemical entities against diseases of national importance :an HTS approach0 aDiscovery of new chemical entities against diseases of national  aCombi Chem-Bio Resource Center, OCD, National Chemical Laboratory, Pune - 411 008cFEB1 aNawale, Laxman1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/discovery-new-chemical-entities-against-diseases-national-importance-hts-approach00931nas a2200121 4500008004100000245008000041210006900121260005100190520042200241100001900663700001900682856010800701 2015 eng d00aEfficacy study of potential anti-tubercular molecules: in-vitro and ex-vivo0 aEfficacy study of potential antitubercular molecules invitro and aNational Chemical Laboratory, Pune 411008cFEB3 a

Tuberculosis: Infectious disease caused by the bacillus Mycobacterium tuberculosis Second leading infectious killer after HIV/AIDS In 2013, 8.6 million TB cases were reported out of which 1.3 million died Emergence of Multi-drug resistant TB (MDR-TB) and extremely drug resistant TB (XDR) for which no drugs are available. Latency being a cause of recurring TB infection is a major problem in eradication of TB

1 aNawale, Laxman1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/efficacy-study-potential-anti-tubercular-molecules-vitro-and-ex-vivo01370nas a2200145 4500008004100000245011400041210006900155260009000224520069800314100001801012700001901030700002601049700001901075856013001094 2015 eng d00aHigh throughput screening of inhibitors for tuberculosis at NCL : a novel drug discovery initiative from CSIR0 aHigh throughput screening of inhibitors for tuberculosis at NCL  aCSIR-National Chemical Laboratory, PunebCSIR-National Chemical Laboratory, PunecSEP3 a

Discover and develop novel drugs that are effective at curing latent, drug sensitive and drug resistant TB Study the biology of tuberculosis bacilli in great detail to identify new metabolic pathways that may be vulnerable to drugs Test thousands of potential drugs in our screening facility to find new compounds or new compound classes that kill TB bacteria Increase throughput up to 20,000 compounds at a time Develop novel screens using conditions that mimic those the TB bacteria encounters in the human body Utilize medical chemistry to optimize the structures of compounds so that they kill TB bacteria in a more potent fashion and are non-toxic Meet the challenges from industry

1 aManek, Hardik1 aNawale, Laxman1 aJadhav, Nandadeep, J.1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/high-throughput-screening-inhibitors-tuberculosis-ncl-novel-drug-discovery-initiative-csir02692nas a2200193 4500008004100000022001400041245011800055210006900173260011000242300001600352490000600368520188100374100002202255700001802277700002402295700001902319700002802338856013202366 2015 eng d a2046-206900aIntrinsic therapeutic and biocatalytic roles of ionic liquid mediated self-assembled platinum-phytase nanospheres0 aIntrinsic therapeutic and biocatalytic roles of ionic liquid med aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcJUL a62871-628810 v53 a

We herein report the inherent antitumor efficiency of self-assembled phytase enzyme nanospheres and enhance their efficiency by decorating with platinum nanoparticles and with the anticancer drug curcumin. Firstly, controlled self-assembly of phytase enzyme in an Ionic Liquid 1-butyl-3-methylimidazolium tetrafluoroborate [Bmim][BF4], led to the formation of therapeutically active phytase nanospheres. These nanospheres were further decorated with platinum nanoparticles by adding the platinum ions to these spheres and the nanoparticles formation was mediated by the specific interaction between the histidine residue (in active site of phytase enzymes) and the platinum ions and subsequent reduction of the ions into nanoparticles. The enzyme spheres act as a functional soft template for the as-formed platinum nanoparticles. These Platinum decorated hybrid biomacromolecular phytase nanospheres were loaded with the anticancer drug curcumin and all the different kinds of nanospheres were subjected to in vitro cytotoxicity for their anticancer effect on three different kinds of cancer cell lines i.e. MCF-7, Hep-G2 and THP-1 derived human macrophages. We observed a gradual increase in the anticancer effect caused by only phytase nanospheres (25%), platinum-phytase nanospheres (37%), phytase-curcumin (78%) and platinum-phytase-curcumin nanospheres (90%) that establishes this protein based system as a robust combinatorial drug delivery vehicle. The platinum-phytase spheres also proved their usability as a highly efficient green and reusable biocatalytic system for phytate degradation. The present work facilitates our understanding of ionic liquid based synthesis for multifunctional protein based drug delivery vehicles incorporating combinatorial chemotherapy for potential application as biopharmaceutical agents for tumor treatment and bio-catalysis.

1 aSoni, Sarvesh, K.1 aSarkar, Sampa1 aSelvakannan, P., R.1 aSarkar, Dhiman1 aBhargava, Suresh, Kumar uhttps://library.ncl.res.in/content/intrinsic-therapeutic-and-biocatalytic-roles-ionic-liquid-mediated-self-assembled-platinum-002190nas a2200193 4500008004100000245010600041210006900147260000800216300001200224490000600236520148400242100002901726700002401755700001901779700002801798700001901826700002101845856013001866 2015 eng d00aLeucas mollissima, a source of bioactive compounds with antimalarial and antimycobacterium activities0 aLeucas mollissima a source of bioactive compounds with antimalar cJAN ae35-e380 v23 a

A phytochemical investigation of the acetone extract from the aerial parts of Leucas mollissima afforded one new (−)epi-marmelo lactone, (2 S, 4R, 6 S)-2,6-dimethyl-6 hydroxy-7-ene-4-olide (1), along with five known compounds, schensianol A (2), vanillin (3), β-hydroxy propiovanillone (4), lanost-9(11),25-diene-3β,24β-diol (5), and lanost-9(11),23E(24)-diene-3β,25-diol (6). Similarly, an investigation of the methanol extract of the aerial parts of L. mollissima resulted in the isolation of three known compounds, (+)-syringaresinol (7), anisofolin A (8), and apigenin 7-O-β-D(− 6′′-p-E-coumaroyl)-glucoside (9). Structure elucidation of the isolated compounds was carried out using detailed analysis of 1D and 2D nuclear magnetic resonance. All compounds were evaluated for antimalarial activity against Plasmodium falciparum (3D7) and for antimycobacterium activity against Mycobacterium tuberculosis H37Ra and Mycobacterium bovis. Compound 8 was found to have promising antimalarial activity (IC50 4.39 ± 0.25 µM), promising antimycobacterium activity [IC50 4.50 ± 0.75 µM (3.31 µg/mL)] against M. tuberculosis H37Ra and at 100 µg/mL, showed 55.6 % inhibition of M. bovis. Compound 9 showed moderate inhibition of P. falciparum growth (35 % inhibition at 10 µM) with respect to the positive control atovaquone and 67.4 % inhibition against M. bovis at 100 µg/mL with respect to the positive control rifampicin.

1 aChinchansure, Ashish, A.1 aArkile, Manisha, A.1 aShukla, Anurag1 aShanmugam, Dhanasekaran1 aSarkar, Dhiman1 aJoshi, Swati, P. uhttps://library.ncl.res.in/content/leucas-mollissima-source-bioactive-compounds-antimalarial-and-antimycobacterium-activities01185nas a2200157 4500008004100000245010300041210006900144260005100213520053400264100001700798700001900815700001900834700001700853700002100870856013600891 2015 eng d00aMechanistic understanding of rapid gelation of silk fibroin using a biosurfactant – sophorolipid0 aMechanistic understanding of rapid gelation of silk fibroin usin aNational Chemical Laboratory, Pune IndiacFEB3 a

3D polymeric hydrogels find use in biomedical applications as scaffolds and drug delivery vehicle • Silk fibroin a structural protein is a promising candidate (excellent thermo-mechanicals, biocompatibility, biodegradability) • Sophorolipid (SL)-a biosurfactant is known to exhibit antimicrobial, anti cancerous and cell differentiating. • Use of SL as gelling agent can enhance the applicability of SF hydrogels • SF-SL scaffolds obtained by lyophilization of hydrogels can find application in tissue regeneration

1 aDubey, Parul1 aNawale, Laxman1 aSarkar, Dhiman1 aNisal, Anuya1 aPrabhune, Asmita uhttps://library.ncl.res.in/content/mechanistic-understanding-rapid-gelation-silk-fibroin-using-biosurfactant-%E2%80%93-sophorolipid01427nas a2200133 4500008004100000245010100041210006900142260000800211490000600219520089900225100001801124700001901142856013201161 2015 eng d00aMultifunctional silica nanoparticles for pancreatic cancer specific drug delivery and bioimaging0 aMultifunctional silica nanoparticles for pancreatic cancer speci cJUN0 v23 a

Mesoporous silica nanoparticles (MSN) have attracted increasing interest as drug carriers due to their biocompatibility and robustness. In this analysis we explored the potential of MSN as nanotheranostic platform for pancreatic cancer specific drug delivery and bioimaging. Pancreatic cancer is the most fatal cancer and due to its high mortality and low prognosis it is imperative to develop new methods for early diagnosis and therapy of this cancer. Though traditionally organic dyes, quantum dots and fluorescent agents are used for bioimaging but here we have utilized graphene quantum dots (GQDs) for bioimaging due to their superior biocompatibility and fluorescence properties. MSN were loaded with gemcitabine; the most preferred drug for pancreatic cancer. MSN and GQDs were characterized by SEM, TEM, FT-IR etc and the efficacy of nanoformulation was determined by MTT assay.

1 aNigam, Preeti1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/multifunctional-silica-nanoparticles-pancreatic-cancer-specific-drug-delivery-and-bioimaging02175nas a2200301 4500008004100000022001400041245010200055210006900157260009200226300001400318490000700332520111600339653001501455653002301470653002201493653001901515653001701534653002201551100002301573700002901596700001901625700001801644700002101662700002401683700001901707700002101726856012601747 2015 eng d a1478-641900aNew butenolide cinnamate and other biological active chemical constituents from Polygonum glabrum0 aNew butenolide cinnamate and other biological active chemical co a4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLANDbTAYLOR & FRANCIS LTDcNOV a2080-20860 v293 a

Phytochemical investigation of the methanol extract of the aerial parts of Polygonum glabrum afforded one new natural product (-)-2-methoxy-2-butenolide-3-cinnamate (1) along with six known compounds, -hydroxyfriedalanol (2), 3-hydroxy-5-methoxystilbene (3), (-) pinocembrin (4), sitosterol-(6-O-palmitoyl)-3-O–d-glucopyranoside (5), (-) pinocembrin-5-methyl ether (6) and sitosterol-3-O–d-glucopyranoside (7). Compound 1 showed promising in vitro anti-HIV-1 activity against primary isolates HIV-1(UG070) (X4, subtype D) and HIV-1(VB59) (R5, subtype C) assayed using TZM-bl cell line with IC50 in the range of 15.68-22.43g/mL. The extract showed TI in the range of 19.19-27.37 with IC50 in the range of 10.90-15.55g/mL. Compounds 1, 3 and 4 exhibited in vitro anti-mycobacterium activity against Mycobacterium tuberculosis H37Ra with IC50 values of 1.43, 3.33 and 1.11g/mL in dormant phase and 2.27, 3.33 and 1.21g/mL in active phase, respectively. Compound 4 was found to be the most active antiproliferative with IC50 values of 1.88-11.00g/mL against THP-1, A549, Panc-1, HeLa and MCF7 cell lines.

10aanti-HIV-110aanti-mycobacterium10aantiproliferative10aphytochemicals10aPolygonaceae10aPolygonum glabrum1 aSaid, Madhukar, S.1 aChinchansure, Ashish, A.1 aNawale, Laxman1 aDurge, Ankita1 aWadhwani, Ashish1 aKulkarni, Smita, S.1 aSarkar, Dhiman1 aJoshi, Swati, P. uhttps://library.ncl.res.in/content/new-butenolide-cinnamate-and-other-biological-active-chemical-constituents-polygonum-001971nas a2200217 4500008004100000022001400041245010800055210006900163260008000232300002400312490000600336520115500342653001301497653002801510653001501538653001701553653001401570100002101584700001901605856012901624 2015 eng d a1664-302X00aQualitative and quantitative proteomic analysis of vitamin C induced changes in mycobacterium smegmatis0 aQualitative and quantitative proteomic analysis of vitamin C ind aPO BOX 110, LAUSANNE, 1015, SWITZERLANDbFRONTIERS RESEARCH FOUNDATIONcMAY aArticle Number: 4510 v63 a

Vitamin C is a critical dietary nutrient in human which has a wide range of regulatory effects on gene expression and physiology of Mycobacterium tuberculosis that leads to a dormant drug-tolerant phenotype. In the presence of iron, vitamin C shows a high bactericidal activity even in the drug resistant phenotype of M. tuberculosis. The regulatory mechanisms underlying vitamin C induced adaptations are largely unknown due to lack of functional genomics data in this field. In this study, we attempt to characterize the direct effect of vitamin C treatment on the physiology of actively growing Mycobacterium smegmatis. The study chose M. smegmatis as it is a fast-growing bacterium and a non-pathogenic model system which shares many physiological features with the pathogenic M. tuberculosis including dormancy and its regulation. The proteomic adaptation of M. smegmatis on vitamin C treatment demonstrates the important changes in cellular and metabolic process such as reversal of tricarboxylic acid cycle, decrease in ATP synthesis, decrease in iron acquisition and storage, and induction of dormancy regulators WhiB3, PhoP, and Lsr2.

10adormancy10aMycobacterium smegmatis10aproteomics10atuberculosis10avitamin C1 aMishra, Abhishek1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/qualitative-and-quantitative-proteomic-analysis-vitamin-c-induced-changes-mycobacterium-101479nas a2200121 4500008004100000245010000041210006900141260009100210520088800301100001901189700001901208856013001227 2015 eng d00aQuantitative, automated, high content screening assay approach to anti-angiogenicdrug discovery0 aQuantitative automated high content screening assay approach to  aCombi Chem-Bio Resource Center, OCD, National Chemical Laboratory, Pune - 411 008cFEB3 a

Angiogenesisenhancescancer,maculardegeneration,etc.. Currentangiogenicassays--indirect,manual,timeconsuming,laborintensive,difficulttoquantify,andexpensive. Wedevelopedanautomated,quantitative,HighContentScreeningangiogenictubeformationassaywouldbenefitdrugdiscoveryforseveraltherapeuticareas. Humanendothelialcellswereseededwithpro-oranti-angiogeniccompoundsonaMatrigelTMlayerina96-wellplate.Afterangiogenictubesformation,thepositivecontrolsandthetestsampleswerefixed,fluorescentlylabeled,automaticallyimagedonCellomics’ArrayScan®HCSReader,andquantitativelyanalyzedon-the-flybytheTubeFormationBioApplicationsoftwaremodule. Multiplefeaturesrelevantforangiogenesisandangiogenictubeformationwereautomaticallymeasured. Thisrobustandreliableassaythusenabledthelarge-scale,quantitative,screeningandcharacterizationofcompoundsaffectingbothpro-andanti-angiogenicpathways.

1 aNawale, Laxman1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/quantitative-automated-high-content-screening-assay-approach-anti-angiogenicdrug-discovery01943nas a2200253 4500008004100000022001400041245012700055210006900182260007600251300001200327490000600339520101400345100002301359700001501382700001801397700002401415700002001439700002201459700002101481700002301502700001901525700002301544856012201567 2015 eng d a1756-891900aRational drug design, synthesis and biological evaluation of dihydrofolate reductase inhibitors as antituberculosis agents0 aRational drug design synthesis and biological evaluation of dihy aUNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLANDbFUTURE SCI LTDcJUN a979-9880 v73 a

Background: A series of 2,4-diamino-s-triazines was designed, with potential for activity against Mycobacterium tuberculosis (Mtb) dihydrofolate reductase enzyme, on the basis of virtual screening results and structure-based drug design. Results: The compounds were evaluated against Mtb (H(37)Rv) and their cytotoxicity was assessed using VERO cell lines. Of particular note, two compounds were found to have the most promising antituberculosis activity (6b minimum inhibitory concentration: 1.76 mu M and 6i minimum inhibitory concentration: 1.57 mu M) along with low cytotoxicity (CC50 : > 300 mu M). The enzyme assay results of these two indicated significant inhibition of Mtb dihydrofolate reductase along with selectivity. Selected derivatives were tested against dormant tubercle bacilli in vivo and ex vivo indicating potential inhibition. Conclusion: This study provides promising antituberculosis dihydrofolate reductase inhibitors that can act as potential leads for further development.

1 aTawari, Nilesh, R.1 aBag, Seema1 aRaju, Archana1 aLele, Arundhati, C.1 aBairwa, Ranjeet1 aRay, Mukti, Kanta1 aRajan, M., G. R.1 aNawale, Laxman, U.1 aSarkar, Dhiman1 aDegani, Mariam, S. uhttps://library.ncl.res.in/content/rational-drug-design-synthesis-and-biological-evaluation-dihydrofolate-reductase-001851nas a2200193 4500008004100000245012800041210006900169260000800238300001200246490000600258520112400264100001901388700002901407700002501436700002401461700001901485700002101504856013201525 2015 eng d00aRottlerin derivatives and other compounds from mallotus philippinensis fruits and their potential antimycobactrial activity0 aRottlerin derivatives and other compounds from mallotus philippi cJUN ae28-e300 v23 a

The methanolic extract of the fruits of Mallotus philippinensis afforded 13 compounds, 7,11-diketo-lanost-3-ol (1, as acetate), lanosta-8-ene-3β-ol (2, as acetate), pregnenolone (3, as acetate), trans-chalcone (4), kamalachalcone E (5), oleanolic acid (6), gallic acid (7), kaempferol (8), myricetin (9), 1-(5,7-dihydroxy-2,2,6-trimethyl-2 H-1-benzopyran-8-yl)-3-phenyl-2-propen-1-one (10), 4′-hydroxyisorottlerin (11), rottlerin (12), and shikimic acid (13). Compound 1 was isolated as a new natural product and its structure was elucidated by 1D and 2D nuclear magnetic resonance analyses including heteronuclear single quantum correlation, heteronuclear multiple-bond correlation, correlation spectroscopy, and nuclear Overhauser effect spectroscopy experiments. All of the isolated compounds were evaluated for their antimycobacterium activity against Mycobacterium tuberculosis H37Ra. Compounds 11 and 12 exhibited promising inhibitory activity with IC50 values of 0.89 ± 0.33 µg/mL (MIC 2.06 ± 0.41 µg/mL) and 7.59 ± 0.42 µg/mL (MIC 11.56 ± 0.35 µg/mL), respectively.

1 aBhardwaj, Rima1 aChinchansure, Ashish, A.1 aKulkarni, Roshan, R.1 aArkile, Manisha, A.1 aSarkar, Dhiman1 aJoshi, Swati, P. uhttps://library.ncl.res.in/content/rottlerin-derivatives-and-other-compounds-mallotus-philippinensis-fruits-and-their-potential01897nas a2200193 4500008004100000022001400041245010500055210006900160260011000229300001600339490000600355520112300361100001701484700001901501700001901520700001701539700002101556856012601577 2015 eng d a2046-206900aSophorolipid assisted tunable and rapid gelation of silk fibroin to form porous biomedical scaffolds0 aSophorolipid assisted tunable and rapid gelation of silk fibroin aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcMAR a33955-339620 v53 a

Three dimensional polymer hydrogels, based on both natural and synthetic polymers, are increasingly being used as scaffolds and drug delivery vehicles for biomedical applications. Fibrous protein, silk fibroin (SF), obtained from the Bombyx mori silkworm is a promising candidate in this area. However, SF has a long gelation time of about a few weeks that can only be reduced by non-physiological treatments (e. g. high temperature, ultrasonication and low pH) or by addition of a chemical and non-biodegradable polymer and/or surfactant. We report here accelerated gelation of SF under physiological conditions using a biosurfactant, sophorolipid (SL) as a gelling agent. SL and SF are completely miscible and form a very clear solution upon mixing. Hence it is interesting to see that this clear solution gels in a time span of just a few hours. The hydrogels so formed have pore architecture, porosities and mechanical stability ideally suited for tissue culture applications. Here we also demonstrate that mouse fibroblast cells not only adhere to but also extensively proliferate on these SF-SL scaffolds.

1 aDubey, Parul1 aNawale, Laxman1 aSarkar, Dhiman1 aNisal, Anuya1 aPrabhune, Asmita uhttps://library.ncl.res.in/content/sophorolipid-assisted-tunable-and-rapid-gelation-silk-fibroin-form-porous-biomedical-001535nas a2200241 4500008004100000022001400041245010100055210006900156260000800225300001400233490000600247520070700253100002500960700002500985700002101010700002201031700002301053700002401076700002601100700002301126700001901149856012501168 2015 eng d a2040-250300aSynthesis and evaluation of thieno[2,3-d]pyrimidin-4(3H)-ones as potential antitubercular agents0 aSynthesis and evaluation of thieno23dpyrimidin43Hones as potenti cAUG a2209-22150 v63 a

A number of thieno[2,3-d]pyrimidin-4(3H)-ones were designed, synthesized and screened against Mycobacteria as a part of our program to develop new antitubercular agents. It was observed that some of the compounds have significant antimycobacterial activity against Mycobacterium tuberculosis H37Ra (ATCC 25177) and Mycobacterium bovis BCG (ATCC 35743). The active compounds were studied for cytotoxicity against four cell lines and were found to be non-cytotoxic. The results showed that compounds 13b and 29e were found to exhibit very good antimycobacterial activity (MIC in the range of 6-8 mu M) and the thienopyrimidinones as a class have potential to be developed as antitubercular agents.

1 aBorate, Hanumant, B.1 aAnnadate, Ritesh, A.1 aVagh, Sandip, S.1 aPisal, Mahesh, M.1 aDeokate, Sagar, B.1 aArkile, Manisha, A.1 aJadhav, Nandadeep, J.1 aNawale, Laxman, U.1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/synthesis-and-evaluation-thieno23-dpyrimidin-43h-ones-potential-antitubercular-agents02428nas a2200301 4500008004100000022001400041245009900055210006900154260006700223300001200290490000700302520136400309653002801673653003301701653001601734653002701750100002101777700002101798700002301819700003401842700001801876700001901894700002201913700002201935700002101957700002401978856012402002 2015 eng d a1747-027700aTargeting dormant tuberculosis bacilli: results for molecules with a novel pyrimidone scaffold0 aTargeting dormant tuberculosis bacilli results for molecules wit a111 RIVER ST, HOBOKEN 07030-5774, NJ USAbWILEY-BLACKWELLcFEB a201-2070 v853 a

Our inability to completely control TB has been due in part to the presence of dormant mycobacteria. This also renders drug regimens ineffective and is the prime cause of the appearance of drug-resistant strains. In continuation of our efforts to develop novel antitubercular agents that especially target dormant mycobacteria, a set of 55 new compounds belonging to the pyrimidone class were designed on the basis of CoMFA and CoMSIA studies, and these were synthesized and subsequently tested against both the dormant and virulent BCG strain of M.tuberculosis. Some novel compounds have been identified which selectively inhibit the dormant tuberculosis bacilli with significantly low IC50 values. This study reports the second molecule after TMC-207, having the ability to inhibit tuberculosis bacilli exclusively in its dormant phase. The synthesis was accomplished by a modified multicomponent Biginelli reaction. A classification model was generated using the binary QSAR approach - recursive partitioning (RP) to identify structural characteristics related to the activity. Physicochemical, structural, topological, connectivity indices, and E-state key descriptors were used for generation of the decision tree. The decision tree could provide insights into structure-activity relationships that will guide the design of more potent inhibitors.

10aAntitubercular activity10adormant tuberculosis bacilli10apyrimidones10arecursive partitioning1 aJoshi, Rohit, R.1 aBarchha, Avinash1 aKhedkar, Vijay, M.1 aPissurlenkar, Raghuvir, R. S.1 aSarkar, Sampa1 aSarkar, Dhiman1 aJoshi, Rohini, R.1 aJoshi, Ramesh, A.1 aShah, Anamik, K.1 aCoutinho, Evans, C. uhttps://library.ncl.res.in/content/targeting-dormant-tuberculosis-bacilli-results-molecules-novel-pyrimidone-scaffold-002112nas a2200241 4500008004100000245013000041210006900171260000800240300001200248490000800260520125600268100002401524700002601548700002601574700002301600700002401623700001801647700001901665700001801684700002001702700001901722856012901741 2016 eng d00aDesign, synthesis and biological evaluation of novel azaspiro analogs of linezolid as antibacterial and antitubercular agents0 aDesign synthesis and biological evaluation of novel azaspiro ana cOCT a475-4870 v1223 a

The design, synthesis and antimicrobial evaluation of a novel series of azaspiro analogues of linezolid (1) have been described. Linezolid comprises of a morpholine ring which is known for its metabolism related liabilities. Therefore, the key modification made in the linezolid structure was the replacement of morpholine moiety with its bioisostere, 2-oxa-6-azaspiro[3.3]heptane. Furthermore, the replacement of N-acetyl terminal of 1 with various aromatic or aliphatic functionalities was carried out. The title compounds were evaluated against a panel of Gram-positive and Gram-negative bacteria and Mycobacterium tuberculosis. Subsequent structure-activity relationship (SAR) studies identified several compounds with mixed antibacterial and antitubercular profiles. Compound 22 (IC50 0.72, 0.51, 0.88, 0.49 mu g/mL for Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, respectively) exhibited similar antibacterial profile as I. The N-acetyl derivative 18 was similar to 1 in antitubercular profile. Thus, the present study successfully demonstrated the use of azaspiro substructure in the medicinal chemistry of antibacterial and antitubercular agents. (C) 2016 Elsevier Masson SAS. All rights reserved.

1 aGadekar, Pradip, K.1 aRoychowdhury, Abhijit1 aKharkar, Prashant, S.1 aKhedkar, Vijay, M.1 aArkile, Manisha, A.1 aManek, Hardik1 aSarkar, Dhiman1 aSharma, Rajiv1 aVijayakumar, V.1 aSarveswari, S. uhttps://library.ncl.res.in/content/design-synthesis-and-biological-evaluation-novel-azaspiro-analogs-linezolid-antibacterial01969nas a2200193 4500008004100000245011800041210006900159260000800228300001400236490000700250520126100257100003001518700002401548700001901572700001701591700001901608700002601627856012201653 2016 eng d00a[Et3NH][HSO4] catalyzed efficient synthesis of 5-arylidene-rhodanine conjugates and their antitubercular activity0 aEt3NHHSO4 catalyzed efficient synthesis of 5arylidenerhodanine c cAUG a6607-66260 v423 a

We have described a highly efficient, safer protocol for the synthesis of 5-arylidene-rhodanine conjugates catalyzed by Bronsted acidic ionic liquid [Et3NH][HSO4] in excellent yields. The protocol offers cost-effective, environmentally benign, solvent-free conditions and recycle-reuse of the catalyst. The synthesized 5-arylidene-rhodanine conjugates were characterized on the basis of (1) H NMR, C-13 NMR and HRMS spectral data. A series of 5-arylidene-rhodanine derivatives 3a-h, 4a-h were synthesized and evaluated for their in vitro antitubercular activity against dormant Mycobacterium tuberculosis H37Ra and M. bovis BCG strains. Moreover, compounds 3a, 3b, 3e, 3f, 3g, 3h and 4f exhibited good antitubercular activity and were also evaluated for anti-proliferative activity against MCF-7, A549 and HCT116 cell lines using modified MTT assay and found to be noncytotoxic. Compounds 3a-h and 4f were further screened for their antibacterial activity against four bacteria strains to assess their selectivity towards M. tuberculosis. Furthermore, in silico ADME prediction of all the tested compounds followed the criteria for orally active drug and, therefore, these compounds may have a good potential for eventual development as oral agents.

1 aSubhedar, Dnyaneshwar, D.1 aShaikh, Mubarak, H.1 aNawale, Laxman1 aYeware, Amar1 aSarkar, Dhiman1 aShingate, Bapurao, B. uhttps://library.ncl.res.in/content/et3nhhso4-catalyzed-efficient-synthesis-5-arylidene-rhodanine-conjugates-and-their01575nas a2200253 4500008004100000022001400041245007200055210006800127260010600195300001400301490000700315520067400322653001900996653001701015653001901032653002801051100003001079700002401109700002401133700001701157700001901174700002601193856010201219 2016 eng d a0960-894X00aFacile synthesis of 1,3-thiazolidin-4-ones as antitubercular agents0 aFacile synthesis of 13thiazolidin4ones as antitubercular agents aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcAPR a1704-17080 v263 a

We have developed, highly efficient, one-pot, solvent-free, [Et3NH][HSO4] catalyzed multicomponent reaction protocol for the synthesis of 1,3-thiazolidin-4-ones in excellent yields. For the first time, the 1,3-thiazolidin-4-ones were evaluated in vitro for their antimycobacterial activity against Mycobacterium tuberculosis dormant MTB H37Ra and Mycobacterium bovis BCG strains. Among the synthesized basic 1,3-thiazolidin-4-ones, particularly the compounds 4c, 4d, 4e, 4f, 4h, 4i and 4j displays promising antitubercular activity along with no significant cytotoxicity against the cell lines MCF-7, A549 and HCT-116. (C) 2016 Elsevier Ltd. All rights reserved.

10aAntitubercular10aCytotoxicity10aGreen protocol10aMulticomponent reaction1 aSubhedar, Dnyaneshwar, D.1 aShaikh, Mubarak, H.1 aArkile, Manisha, A.1 aYeware, Amar1 aSarkar, Dhiman1 aShingate, Bapurao, B. uhttps://library.ncl.res.in/content/facile-synthesis-13-thiazolidin-4-ones-antitubercular-agents-100522nas a2200133 4500008004100000245007500041210006900116260002000185100002500205700001700230700002200247700001900269856010000288 2016 eng d00aGraphene quantum dots - from emergence to nanotheranostic applications0 aGraphene quantum dots from emergence to nanotheranostic applicat aCroatiabIntech1 aJoshi, Preeti, Nigam1 aKundu, Subir1 aSanghi, Sunil, K.1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/graphene-quantum-dots-emergence-nanotheranostic-applications03045nas a2200229 4500008004100000245017800041210006900219260000800288300001400296490000700310520219500317100001502512700001602527700001902543700002302562700002102585700001902606700002102625700002502646700001702671856012702688 2016 eng d00aGSH Induced controlled release of levofloxacin from a purpose-built prodrug: luminescence response for probing the drug release in escherichia coli and staphylococcus aureus0 aGSH Induced controlled release of levofloxacin from a purposebui cSEP a2062-20700 v273 a

Fluoroquinolones are third-generation broad spectrum bactericidal antibiotics and work against both Gram-positive and Gram-negative bacteria. Levofloxacin (L), a fluoroquinolone, is widely used in anti-infective chemotherapy and treatment of urinary tract infection and pneumonia. The main pathogen for urinary tract infections is Escherichia colt, and Streptococcus pneumoniae is responsible for pneumonia, predominantly a lower respiratory tract infection. Poor permeability of L leads to the use of higher dose of this drug and excess drug in the outer cellular fluid leads to central nervous system (CNS) abnormality. One way to counter this is to improve the lipophilicity of the drug molecule, and accordingly, we have synthesized two new Levofloxacin derivatives, which participated in the spatiotemporal release of drug via disulfide bond cleavage induced by glutathione (GSH). Recent studies with Streptococcus mutants suggest that it is localized in epithelial lining fluid (ELF) of the normal lower respiratory tract and the effective [GSH] in ELF is similar to 430 mu M. E. coli typically cause urinary tract infections and the concentration of GSH in porcine bladder epithelium is reported as 0.6 mM for a healthy human. Thus, for the present study we have chosen two important bacteria (Gram + ve and Gram - ve), which are operational in regions having high extracellular GSH concentration. Interestingly, this supports our design of new lipophilic Levofloxacin based prodrugs, which released effective drug on reaction with GSH. Higher lipophilicity favored improved uptake of the prodrugs. Site specific release of the drug (L) could be achieved following a glutathione mediated biochemical transformation process through cleavage of a disulfide bond of these purpose-built prodrugs. Further, appropriate design helped us to demonstrate that it is possible also to control the kinetics of the drug release from respective prodrugs. Associated luminescence enhancement helps in probing the release of the drug from the prodrug in bacteria and helps in elucidating the mechanistic pathway of the transformation. Such an example is scarce in the contemporary literature.

1 aPal, Suman1 aRamu, Vadde1 aTaye, Nandaraj1 aMogare, Devraj, G.1 aYeware, Amar, M.1 aSarkar, Dhiman1 aReddy, Srinivasa1 aChattopadhyay, Samit1 aDas, Amitava uhttps://library.ncl.res.in/content/gsh-induced-controlled-release-levofloxacin-purpose-built-prodrug-luminescence-response01733nas a2200205 4500008004100000245011600041210006900157260000800226300001400234490000700248520098800255100002401243700002501267700002301292700002401315700002301339700001901362700001901381856012701400 2016 eng d00aIn vitro and ex vivo antitubercular activity of diarylheptanoids from the rhizomes of alpinia officinarum hance0 aIn vitro and ex vivo antitubercular activity of diarylheptanoids cMAR a2825-28300 v303 a

Phytochemical investigation of methanol extract of the rhizomes of Alpinia officinarum Hance afforded four known diarylheptanoids 1,7-diphenylhept-4-en-3-one (1), 5-hydroxy-1,7-diphenyl-3-heptanone (2), 5-hydroxy-7-(4 ''-hydroxy-3 ''-methoxyphenyl)-1-phenyl-3-heptanone (3), and 7-(4 ''-hydroxy-3 ''-methoxyphenyl)-1-phenyl heptan-3-one (4).The acetate derivative of (4), 7-(4 ''-actetate-3 ''-methoxy phenyl)-1-phenyl heptan-3-one (5), was prepared. These diarylheptanoids exhibited promising in vitro and ex vivo antitubercular activity for the first time against dormant Mycobacterium tuberculosis H37Ra with the IC50 values between 0.3447.69 and 0.1322.91 mu M, respectively. All compounds showed comparable activity against Mycobacterium bovis BCG (dormant phage) and did not show any activity against two gram + ve and two gram -ve bacterial strains. These compounds were also weakly cytotoxic up to 300 mu M against three human cancer cell lines THP-1, Panc-1 and A549.

1 aHonmore, Varsha, S.1 aRojatkar, Supada, R.1 aNawale, Laxman, U.1 aArkile, Manisha, A.1 aKhedkar, Vijay, M.1 aNatu, Arun, D.1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/vitro-and-ex-vivo-antitubercular-activity-diarylheptanoids-rhizomes-alpinia-officinarum03545nas a2200313 4500008004100000022001400041245013800055210006900193260007300262300000900335490000700344520238000351653007102731653002402802653002202826653001602848653002102864653001302885100002402898700002302922700002102945700002302966700001902989700002703008700002203035700002503057700001903082856013003101 2016 eng d a1567-576900aIsolates of alpinia officinarum hance as COX-2 inhibitors: evidence from anti-inflammatory, antioxidant and molecular docking studies0 aIsolates of alpinia officinarum hance as COX2 inhibitors evidenc aPO BOX 211, 1000 AE AMSTERDAM, NETHERLANDSbELSEVIER SCIENCE BVcAPR a8-170 v333 a

Background: Inflammation triggered by oxidative stress can cause various ailments, such as cancer, rheumatoid arthritis, asthma, diabetes etc. In the last few years, there has been a renewed interest in studying the antioxidant and anti-inflammatory action of plant constituents such as flavonoids and diarylheptanoids. Aim: To evaluate the antioxidant, anti-inflammatory activity and the total phenolic content of isolated compounds from Alpinia officinarum rhizomes. Furthermore, molecular docking was performed to study the binding mode of these compounds into the active site of cyclooxygenase-2 (COX -2). Methods: A. officinarum rhizomes were extracted by maceration, using methanol. This extract was further fractionated by partitioning with hexane, chloroform and ethyl acetate and these fractions on further purification resulted in isolation of five pure compounds. Characterization was carried out by using H-1 NMR, C-13 NMR and MS. They were further evaluated for antioxidant and anti-inflammatory activity using carrageenan-induced paw edema model in rats. Molecular docking study was performed using Glide module integrated in Schrodinger molecular modeling software. Results: The compounds were identified as 1,7-diphenylhept-4-en-3-one (1), 5-hydroxy-1,7-diphenyl-3-heptanone (2), 3,5,7-trihydroxyflavone (Galangin, 3), 3,5,7-trihydroxy-4'-methoxyflavone (Kaempferide, 4) and 5-hydroxy-7-(4 `'-hydroxy-3 `'-methoxyphenyl)-1-phenyl-3-heptanone (5). The compound-3 and compound-5 (10 mg/kg) showed significant (p < 0.001) antioxidant and anti-inflammatory potential. Moreover, total phenolic content was detected as 72.96 mg and 51.18 mg gallic acid equivalent respectively. All the five isolates were found to be good binders with COX-2 (average docking score -9.03). Conclusions: Galangin and 5-hydroxy-7-(4 `'-hydroxy-3 `'-methoxyphenyl)-1-phenyl-3-heptanone exhibited anti-inflammatory and in-vitro antioxidant activity which may be due to presence of phenolic content in it. The molecular docking study revealed that these compounds have affinity towards COX-2 active site which can further be explored as selective COX-2 inhibitors. The results obtained in this work justify the use of A. officinarum in the treatment of inflammatory disorders like rheumatoid arthritis and inflammatory bowel diseases. (C) 2016 Elsevier B.V. All rights reserved.

10a5-Hydroxy-7-(4 `'-hydroxy-3 `'-methoxyphenyl)-1-phenyl-3-heptanone10aAlpinia officinarum10aAnti-inflammatory10aAntioxidant10aCOX-2 inhibitors10aGalangin1 aHonmore, Varsha, S.1 aKandhare, Amit, D.1 aKadam, Parag, P.1 aKhedkar, Vijay, M.1 aSarkar, Dhiman1 aBodhankar, Subhash, L.1 aZanwar, Anand, A.1 aRojatkar, Supada, R.1 aNatu, Arun, D. uhttps://library.ncl.res.in/content/isolates-alpinia-officinarum-hance-cox-2-inhibitors-evidence-anti-inflammatory-antioxidant01752nas a2200169 4500008004100000245017100041210006900212260000800281300001200289490000600301520106100307100002401368700002401392700001901416700002801435856011901463 2016 eng d00aNaturally occurring anti-TB agents: isolation, chemical transformations and in vitro antitubercular activities of secondary metabolites of rhizomes of alpinia galanga0 aNaturally occurring antiTB agents isolation chemical transformat cSEP ae55-e590 v33 a

A bioactivity-guided chemical examination of the acetone extract of the rhizomes of Alpinia galanga led to the isolation of six sec-ondary metabolites, eucalyptol derivative (1)andphenylpropa-noids (2–6). The structures of all of the isolated compounds (1–6)wereelucidatedonthebasisoftheirspectraldata.Theisolatedcompounds (1–6)werein vitro assayed against active and dor-mant phenotypes of Mycobacterium tuberculosis H37Ra, respec-tively. Interestingly, 1′S-1′-acetoxychavicol acetate (2)showedgood antitubercular activities against both active and dormantphenotypes of M. tuberculosis with IC50 values of 1.04 µM and2.69 µM, respectively. Tsuji-Trost and homodimerization reac-tions of the active compound (2)respectivelyresultedinthefor-mation of two analogues, 7and 8.Bothofthesesynthesizedana-logues were also found to be active in vitro against active [IC50 sof3.24 and 3.87 µM, respectively, for compounds 7and 8]anddor-mant [IC50 sof8.33and2.41µM,respectively,forcompounds7and 8]phenotypesofM. tuberculosis H37Ra, respectively.

1 aValkute, Tushar, R.1 aArkile, Manisha, A.1 aSarkar, Dhiman1 aBhattacharya, Asish, K. uhttps://library.ncl.res.in/content/naturally-occurring-anti-tb-agents-isolation-chemical-transformations-and-vitro01917nas a2200181 4500008004100000245011400041210006900155260000800224300001200232490000600244520124400250100002901494700002401523700002301547700001901570700002101589856012501610 2016 eng d00aNew dinor-cis-labdane diterpene and flavonoids with antimycobacterium activity from colebrookea oppositifolia0 aNew dinorcislabdane diterpene and flavonoids with antimycobacter cMAR ae20-e240 v33 a

The new 14,15-dinor-cis-labdane diterpene, named (+)-14,15-dinor-9α-hydroxy-cis-labd-11(E)-en-13-one (1), was isolated from the acetone extract of the aerial parts of Colebrookea oppositifolia, along with the known compounds alnustin (2), mosloflavone (3), flindulatin (4), 5,6,7-trimethoxy baicalein (5), tanetin (6), scutellarein 4′-methyl ether (7), apigenin (8), caffeic acid (9), anisofolin A (10), apigetrin (11), and forsythoside A (12). Structures of the new and known compounds were established by detailed analysis of 1D and 2D nuclear magnetic resonance studies. The isolated compounds 1–12 were evaluated for their antimycobacterium activity against Mycobacterium tuberculosis H37Ra and Mycobacterium bovis in both dormant and active phases. Compounds 1, 7, and 8 exhibited inhibitory activity against M. tuberculosis with IC50 values in the range of 8.1–55.0 µM (MIC 14.4–119.7 µM) in the active phase and 7.4–43.5 µM (MIC 11.5–123.3 µM) in the dormant phase. Similarly 1, 7, and 8 exhibited inhibitory activity against M. bovis with IC50 values in the range of 4.1–98.5 µM (MIC 13.7–161.0 µM) in the active phase and 4.1–111.1 µM (MIC 13.0–166.4 µM) in the dormant phase.

1 aChinchansure, Ashish, A.1 aArkile, Manisha, A.1 aShinde, Dinesh, R.1 aSarkar, Dhiman1 aJoshi, Swati, P. uhttps://library.ncl.res.in/content/new-dinor-cis-labdane-diterpene-and-flavonoids-antimycobacterium-activity-colebrookea01812nas a2200265 4500008004100000022001400041245009900055210006900154260009200223300001200315490000700327520083500334653002101169653003001190653003101220653001501251653001401266100002501280700002101305700002301326700002601349700001901375700002101394856013101415 2016 eng d a1478-641900aNew pimarane diterpenes and other antimycobacterial metabolites from anisochilus verticillatus0 aNew pimarane diterpenes and other antimycobacterial metabolites  a4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLANDbTAYLOR & FRANCIS LTDcMAR a675-6810 v303 a

Phytochemical investigation of the acetone extract of the aerial parts of Anisochilus verticillatus afforded a new 8,9-secopimarane diterpene (1), two new isopimarane diterpenes (2, 3) and the known ursolic acid (4), beta-amyrin (5), -amyrin (6), stigmast-5-en-3-one (7) and hydroxychavicol (8). Structures of the new compounds were elucidated with the help of 1D and 2D nuclear magnetic resonance spectroscopic data, and single crystal X-ray crystallography of compound 3. Compounds 2 and 8 inhibited Mycobacterium tuberculosis H37Ra with an IC50 of 11.3 (IC90 of 20.0g/mL) and 12.5g/mL, respectively. Correspondingly, molecular docking studies with Extra Precision Glide revealed a correlation between score and biological activity for these compounds to describe the molecular basis for the most significant SAR results.

10aalanine racemase10aAnisochilus verticillatus10aantimycobacterial activity10aditerpenes10aLamiaceae1 aKulkarni, Roshan, R.1 aShurpali, Ketaki1 aKhedkar, Vijay, M.1 aPuranik, Vedavati, G.1 aSarkar, Dhiman1 aJoshi, Swati, P. uhttps://library.ncl.res.in/content/new-pimarane-diterpenes-and-other-antimycobacterial-metabolites-anisochilus-verticillatus-002255nas a2200289 4500008004100000022001400041245010400055210006900159260010600228300001400334490000700348520119600355653001501551653001901566653001701585653001801602653002601620100003001646700002401676700001901700700001701719700001901736700002601755700003101781700002601812856012701838 2016 eng d a0960-894X00aNovel tetrazoloquinoline-rhodanine conjugates: highly efficient synthesis and biological evaluation0 aNovel tetrazoloquinolinerhodanine conjugates highly efficient sy aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcMAY a2278-22830 v263 a

In search of new active molecules against Mycobacterium tuberculosis (MTB) H37Ra and Mycobacterium bovis BCG, a small focused library of rhodanine incorporated tetrazoloquinoline has been efficiently synthesized by using [HDBU][HSO4] acidic ionic liquid. The compound 3c found to be promising inhibitor of MTB H37Ra and M. bovis BCG characterized by lower MIC values 4.5 and 2.0 mu g/mL, respectively. The active compounds were further tested for cytotoxicity against HeLa, THP-1, A549 and PANC-1 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Again, the synthesized compounds were found to have potential antifungal activity. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against a potential target Zmp1 enzyme of MTB H37Ra, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of in vitro and in silico study suggest that these compounds possess ideal structural requirement for the further development of novel therapeutic agents. (C) 2016 Elsevier Ltd. All rights reserved.

10aantifungal10aAntitubercular10aCytotoxicity10aDocking study10aRhodanine derivatives1 aSubhedar, Dnyaneshwar, D.1 aShaikh, Mubarak, H.1 aNawale, Laxman1 aYeware, Amar1 aSarkar, Dhiman1 aKhan, Firoz, A. Kalam1 aSangshetti, Jaiprakash, N.1 aShingate, Bapurao, B. uhttps://library.ncl.res.in/content/novel-tetrazoloquinoline-rhodanine-conjugates-highly-efficient-synthesis-and-biological01988nas a2200193 4500008004100000245012200041210006900163260000800232300001400240490000600254520126200260100003001522700002401552700002601576700001901602700001901621700002301640856013101663 2016 eng d00aNovel tetrazoloquinoline-thiazolidinone conjugates as possible antitubercular agents: synthesis and molecular docking0 aNovel tetrazoloquinolinethiazolidinone conjugates as possible an cJUL a1832-18480 v73 a

A novel approach for the synthesis of a new 4-thiazolidinone scaffold was developed by a one-pot three-component cyclocondensation of various tetrazolo quinoline aldehydes 1a-f, acid hydrazide 2a-c, and thioglycolic acid 3 in the presence of [DBUH].OAc] as a catalyst in high yields. All the conjugates were screened for their antimycobacterial activity against MTB H37Ra and M. bovis BCG strains, with the MIC values ranging from 0.99-13.55 mu mol mL(-1) and 0.14-20.11 mu mol mL(-1), respectively. The 4-thiazolidinone-incorporated tetrazoloquinoline derivatives 4a, 4d, 4g, 4j, 4m, and 4p were highly potent against MTB H37Ra and M. bovis BCG strains. The most active compounds were also evaluated for their cytotoxicity against MCF-7, A549, and HCT 116 cell lines and were found to be non-cytotoxic. Further, molecular docking studies into the active site of the InhA enzyme revealed a similar binding mode to the native ligand in the crystal structure, thereby helping us to understand the ligand-protein binding interaction and establish a structural basis for the inhibition of mycobacterium tuberculosis. The results suggest that the tetrazoloquinoline-thiazolidinone conjugates 4a, 4d, 4g, 4j, 4m, and 4p are promising antitubercular agents.

1 aSubhedar, Dnyaneshwar, D.1 aShaikh, Mubarak, H.1 aShingate, Bapurao, B.1 aNawale, Laxman1 aSarkar, Dhiman1 aKhedkar, Vijay, M. uhttps://library.ncl.res.in/content/novel-tetrazoloquinoline-thiazolidinone-conjugates-possible-antitubercular-agents-synthesis03131nas a2200301 4500008004100000022001400041245008900055210006900144260008400213300001600297490000700313520210200320653002802422653001702450653002002467653001702487653001802504653001702522100001702539700001902556700002402575700002102599700002502620700002002645700001902665700002602684856011902710 2016 eng d a1178-201300aPhytogenic silver, gold, and bimetallic nanoparticles as novel antitubercular agents0 aPhytogenic silver gold and bimetallic nanoparticles as novel ant aPO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALANDbDOVE MEDICAL PRESS LTDcMAY a1889—18970 v113 a

Purpose: Multi- and extensively drug-resistant tuberculosis (TB) is a global threat to human health. It requires immediate action to seek new antitubercular compounds and devise alternate strategies. Nanomaterials, in the present scenario, have opened new avenues in medicine, diagnosis, and therapeutics. In view of this, the current study aims to determine the efficacy of phytogenic metal nanoparticles to inhibit mycobacteria. Methods: Silver (AgNPs), gold (AuNPs), and gold-silver bimetallic (Au-AgNPs) nanoparticles synthesized from medicinal plants, such as Barleria prionitis, Plumbago zeylanica, and Syzygium cumini, were tested against Mycobacterium tuberculosis and M. bovis BCG. In vitro and ex vivo macrophage infection model assays were designed to determine minimum inhibitory concentration (MIC) and half maximal inhibitory concentration of nanoparticles. Microscopic analyses were carried out to demonstrate intracellular uptake of nanoparticles in macrophages. Besides this, biocompatibility, specificity, and selectivity of nanoparticles were also established with respect to human cell lines. Results: Au-AgNPs exhibited highest antitubercular activity, with MIC of <2.56 mu g/mL, followed by AgNPs. AuNPs did not show such activity at concentrations of up to 100 mu g/mL. In vitro and ex vivo macrophage infection model assays revealed the inhibition of both active and dormant stage mycobacteria on exposure to Au-AgNPs. These nanoparticles were capable of entering macrophage cells and exhibited up to 45% cytotoxicity at 30 mu g/mL (ten times MIC concentration) after 48 hours. Among these, Au-AgNPs synthesized from S. cumini were found to be more specific toward mycobacteria, with their selectivity index in the range of 94-108. Conclusion: This is the first study to report the antimycobacterial activity of AuNPs, AgNPs, and Au-AgNPs synthesized from medicinal plants. Among these, Au-AgNPs from S. cumini showed profound efficiency, specificity, and selectivity to kill mycobacteria. These should be investigated further to develop novel TB nanoantibiotics.

10aAntimycobacterial agent10aCytotoxicity10adrug resistance10aMycobacteria10aNanoparticles10atuberculosis1 aSingh, Richa1 aNawale, Laxman1 aArkile, Manisha, A.1 aWadhwani, Sweety1 aShedbalkar, Utkarsha1 aChopade, Snehal1 aSarkar, Dhiman1 aChopade, Balu, Ananda uhttps://library.ncl.res.in/content/phytogenic-silver-gold-and-bimetallic-nanoparticles-novel-antitubercular-agents02057nas a2200241 4500008004100000022001400041245009800055210006900153260007300222300001200295490000700307520118200314653001901496653001401515653002801529653002401557100002501581700001801606700001901624700001901643700002301662856013001685 2016 eng d a0141-813000aShape and size engineered cellulosic nanomaterials as broad spectrum anti-microbial compounds0 aShape and size engineered cellulosic nanomaterials as broad spec aPO BOX 211, 1000 AE AMSTERDAM, NETHERLANDSbELSEVIER SCIENCE BVcJUN a460-4650 v873 a

Oxidized celluloses have been used for decades as antimicrobial wound gauzes and surgical cotton. We now report the successful synthesis of a next generation narrow size range (25-35 nm) spherical shaped nanoparticles of 2,3,6-tricarboxycellulose based on cellulose I structural features, for applications as new antimicrobial materials. This study adds to our previous study of 6-carboxycellulose. A wide range of bacteria such as Escherichia coli, Staphloccocus aureus, Bacillus subtilis and Mycobacterium tuberculosis (non-pathogenic as well as pathogenic strains) were affected by these polymers in in vitro studies. Activity against Mycobacteria were noted at high concentrations (MIC99 values 250-1000 mu g/ml, as compared to anti-TB drug Isoniazid 0.3 mu g/ml). However, the broad spectrum activity of oxidized celluloses and their nanoparticles against a wide range of bacteria, including Mycobacteria, show that these materials are promising new biocompatible and biodegradable drug delivery vehicles wherein they can play the dual role of being a drug encapsulant as well as a broad spectrum anti-microbial and anti-TB drug. (C) 2016 Published by Elsevier B.V.

10aAnti-microbial10acellulose10aSpherical nanoparticles10aTricarboxycellulose1 aSharma, Priyanka, R.1 aKamble, Sunil1 aSarkar, Dhiman1 aAnand, Amitesh1 aVarma, Anjanikumar uhttps://library.ncl.res.in/content/shape-and-size-engineered-cellulosic-nanomaterials-broad-spectrum-anti-microbial-compounds02321nas a2200313 4500008004100000022001400041245010700055210006900162260010600231300001400337490000700351520123800358653000601596653000601602653001701608653002801625653001701653653002201670653001301692653001301705100002501718700002701743700002401770700002301794700002301817700001901840700002101859856012701880 2016 eng d a0960-894X00aSynthesis and antitubercular activity of new 1,3,4-oxadiazoles bearing pyridyl and thiazolyl scaffolds0 aSynthesis and antitubercular activity of new 134oxadiazoles bear aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcAUG a3646-36510 v263 a

In search of more potent and safe new antitubercular agents, here new 2-pyridinyl substituted thiazolyl-5-aryl-1,3,4-oxadiazoles (6a-o), have been designed and synthesized using thionicotinamide as a starting, following novel multistep synthetic route. An intermediate, pyridinyl substituted thiazolyl acid hydrazide (4) when condensed with benzoic acids/nicotinic acids (5a-o) in the presence of silica supported POCl3 yielded better to excellent yields of the title compounds. All the synthesized compounds (6a-o) and intermediate acid hydrazide (4) have been screened for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG. Amongst them, 6f, 6j, 6l and 6o have revealed promising activity against M. bovis BCG at concentrations less than 3 mu g/mL. These compounds have shown low cytotoxicity (CC50: > 100 mu g/mL) towards four human cancer cell lines. Molecular docking study has also been performed against mycobacterial enoyl reductase (InhA) enzyme to gain an insight into the binding modes of these molecules and recorded good binding affinity. The ADME properties the title products have also been analyzed. (C) 2016 Elsevier Ltd. All rights reserved.

10a110a310a4-Oxadiazole10aAntitubercular activity10aCytotoxicity10aMolecular docking10aPyridine10aThiazole1 aDhumal, Sambhaji, T.1 aDeshmukh, Amarsinh, R.1 aBhosle, Manisha, R.1 aKhedkar, Vijay, M.1 aNawale, Laxman, U.1 aSarkar, Dhiman1 aMane, Ramrao, A. uhttps://library.ncl.res.in/content/synthesis-and-antitubercular-activity-new-134-oxadiazoles-bearing-pyridyl-and-thiazolyl02318nas a2200265 4500008004100000022001400041245006800055210006600123260007100189300001200260490000600272520144900278653002201727653001701749653001701766653001201783653002201795100002401817700002201841700002301863700002301886700001901909700002601928856009801954 2016 eng d a1948-587500aSynthesis and antitubercular activity of new benzo[b]thiophenes0 aSynthesis and antitubercular activity of new benzobthiophenes a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcAUG a751-7560 v73 a

In vitro and ex vivo efficacies of four series of benzo[b]thiophene-2-carboxylic acid derivatives were studied against Mycobacterium tuberculosis H37Ra (MTB). Benzo[b]thiophenes were also tested in vitro against multidrug resistant Mycobacterium tuberculosis H37Ra (MDR-MTB), and 7b was found to be highly active against A- and DMDR-MTB/MTB (MIC ranges 2.73-22.86 mu g/mL). The activity of all benzo[b]-thiophenes against M. bovis BCG (BCG) was also assessed grown under aerobic and under conditions of oxygen depletion. Compounds 8c and 8g showed significant activity with MICs of 0.60 and 0.61 mu g/mL against dormant BCG. The low cytotoxicity and high selectivity index data against human cancer cell lines, HeLa, Panc-1, and THP-1 indicate the potential importance of the development of benzo[b]thiophene-based 1,3-diketones and flavones as lead candidates to treat mycobacterial infections. Molecular docking studies into the active site of DprE1 (Decaprenylphosphoryl-beta-n-ribose-2'-epimerase) enzyme revealed a similar binding mode to native ligand in the crystal structure thereby helping to understand the ligand protein interactions and establish a structural basis for inhibition of MTB. In summary, its good activity in in vitro and ex vivo model, as well as its activity against multidrug-resistant M. tuberculosis H37Ra in a potentially latent state, makes 7b an attractive drug candidate for the therapy of tuberculosis.

10aBenzo[b]thiophene10aCytotoxicity10aM. Bovis BCG10aMDR-MTB10aMolecular docking1 aMahajan, Pravin, S.1 aNikam, Mukesh, D.1 aNawale, Laxman, U.1 aKhedkar, Vijay, M.1 aSarkar, Dhiman1 aGill, Charansingh, H. uhttps://library.ncl.res.in/content/synthesis-and-antitubercular-activity-new-benzobthiophenes02397nas a2200301 4500008004100000022001400041245012900055210006900184260010600253300001200359490000700371520132200378653000601700653000601706653001501712653002001727653001601747653001901763653001801782100002401800700003001824700002401854700002301878700002601901700001901927700002601946856012301972 2016 eng d a0960-894X00aSynthesis and bioactivity of novel triazole incorporated benzothiazinone derivatives as antitubercular and antioxidant agent0 aSynthesis and bioactivity of novel triazole incorporated benzoth aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcJAN a561-5690 v263 a

In search of new active molecules against Mycobacterium tuberculosis (MTB) H37Ra and M. bovis BCG, a small focused library of benzothiazinone based 1,2,3-triazoles has been efficiently prepared via click chemistry approach. Several derivatives were found to be promising inhibitors of MTB and M. bovis BCG characterized by lower MIC values (27.34-29.37 mu g/mL). Among all the synthesized compounds, 6c and 6e is the most active compound against MTB and M. bovis BCG. The compounds were further tested for anti-proliferative activity against HeLa, A549 and A431 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Further, the synthesized compounds were found to have potential antioxidant activity with IC50 range = 14.14-47.11 mu g/mL. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against a potential target MTB DprE1, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of the in vitro and in silico study suggest that the triazole incorporated benzothiazinone may possess the ideal structural requirements for further development of novel therapeutic agents. (C) 2015 Elsevier Ltd. All rights reserved.

10a110a210a3-Triazole10aADME prediction10aAntioxidant10aAntitubercular10aDocking study1 aShaikh, Mubarak, H.1 aSubhedar, Dnyaneshwar, D.1 aArkile, Manisha, A.1 aKhedkar, Vijay, M.1 aJadhav, Nandadeep, J.1 aSarkar, Dhiman1 aShingate, Bapurao, B. uhttps://library.ncl.res.in/content/synthesis-and-bioactivity-novel-triazole-incorporated-benzothiazinone-derivatives-002327nas a2200313 4500008004100000022001400041245010800055210006900163260010600232300001400338490000700352520125400359653001201613653001201625653001801637653001301655653001901668653001701687100001901704700002201723700002001745700001901765700002401784700001501808700001901823700002301842700002101865856012701886 2016 eng d a0960-894X00aSynthesis and docking studies of pyrazine-thiazolidinone hybrid scaffold targeting dormant tuberculosis0 aSynthesis and docking studies of pyrazinethiazolidinone hybrid s aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcMAY a2224-22280 v263 a

The persistence of Mycobacterium tuberculosis (MTB) in dormant stage assists the pathogen to develop resistance against current antimycobactrial drugs. To address this issue, we report herein the synthesis of N-(4-oxo-2 substituted thiazolidin-3yl) pyrazine-2-carbohydrazide derivatives designed by following the molecular hybridization approach using pyrazine and thiazolidenone scaffolds. The compounds were evaluated against MTB H37Ra and Mycobacterium bovis BCG in dormancy model. Most of the compounds had IC50 values in 0.3-1 mu g/ml range. The active compounds were further tested for anti-proliferative activity against THP-1, Panc-1, A549, and MCF-7 cell lines using MTT assay and exhibited no significant cytotoxicity. We also report molecular docking studies using active analogs and MTB Decaprenylphosphoryl-beta-D-ribose-2'-epimerase (DprE1) to rationalize the biological activity and to provide an insight into the probable mechanism of action and binding mode of hybridized structures. The results obtained validate the use of molecular hybridization approach and also suggest that reported compounds can provide a novel pharmacophore to synthesize lead compounds against dormat MTB. (C) 2016 Elsevier Ltd. All rights reserved.

10adocking10aDormant10aHybrid design10aPyrazine10aThiazolidenone10atuberculosis1 aChitre, T., S.1 aAsgaonkar, K., D.1 aMiniyar, P., B.1 aDharme, A., B.1 aArkile, Manisha, A.1 aYeware, A.1 aSarkar, Dhiman1 aKhedkar, Vijay, M.1 aJha, Prakash, C. uhttps://library.ncl.res.in/content/synthesis-and-docking-studies-pyrazine-thiazolidinone-hybrid-scaffold-targeting-dormant00941nas a2200229 4500008004100000022001400041245012400055210006900179260011000248300000800358490000600366100002500372700002500397700002100422700002200443700002300465700002400488700002600512700002300538700001900561856013100580 2016 eng d a2040-250300aSynthesis and evaluation of thieno[2,3-d]pyrimidin-4(3H)-ones as potential antitubercular agents (vol 6, pg 2209, 2015)0 aSynthesis and evaluation of thieno23dpyrimidin43Hones as potenti aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcDEC a3790 v71 aBorate, Hanumant, B.1 aAnnadate, Ritesh, A.1 aVagh, Sandip, S.1 aPisal, Mahesh, M.1 aDeokate, Sagar, B.1 aArkile, Manisha, A.1 aJadhav, Nandadeep, J.1 aNawale, Laxman, U.1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/synthesis-and-evaluation-thieno23-dpyrimidin-43h-ones-potential-antitubercular-agents-vol-102288nas a2200301 4500008004100000022001400041245007900055210006900134260009500203300001100298490000700309520124200316653003201558653003101590653001601621653001601637653002601653653002001679100002001699700001601719700001901735700001901754700002001773700002001793700002701813700003301840856011301873 2016 eng d a0045-206800aSynthesis and tyrosinase inhibition activity of trans-stilbene derivatives0 aSynthesis and tyrosinase inhibition activity of transstilbene de a525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USAbACADEMIC PRESS INC ELSEVIER SCIENCEcFEB a97-1020 v643 a

Synthesis of a focussed library of trans-stilbene compounds through Wittig and other base catalysed condensation reactions is presented. The synthesized stilbenes were screened for their inhibitory potential against murine tyrosinase activity to explore the structure activity relationship (SAR). Presence of electron withdrawing group (-CN) at the double bond and hydroxyl group or halogen atom especially at para-position on the aromatic rings was found to significantly elevate the inhibitory activity. Among all the compounds screened, compounds 2, 6, 8, 10, 11, 15 and 21 were found to exhibit appreciable inhibitory activity. Compound 21 ((E)-2,3-bis(4-Hydroxyphenyl) acryonitrile) was found to be the most active with an IC50 value of 5.06 mu M which is less than half of the value 10.78 mu M observed for resveratrol (common standard used in murine tyrosinase activity studies) under similar conditions. The results obtained from the present study reveal structural/functional group sensitivity for the tyrosinase inhibitory activity of stilbenoid moieties and are expected to be very helpful for the design and synthesis of novel, selective and effective tyrosinase inhibitors. (C) 2016 Elsevier Inc. All rights reserved.

10aElectron withdrawing groups10aMurine tyrosinase activity10aResveratrol10aStilbenoids10aTyrosinase inhibitors10aWittig reaction1 aIsmail, Tabasum1 aShafi, Syed1 aSrinivas, Jada1 aSarkar, Dhiman1 aQurishi, Yasrib1 aKhazir, Jabeena1 aAlam, Mohammad, Sarwar1 aKumar, Halmuthur, Mahabalara uhttps://library.ncl.res.in/content/synthesis-and-tyrosinase-inhibition-activity-trans-stilbene-derivatives-002733nas a2200361 4500008004100000022001400041245015600055210006900211260008300280300001200363490000700375520148300382653000601865653000601871653001501877653002001892653001801912653001601930653001901946653002001965653001801985100002402003700003002027700002602057700002602083700003102109700002302140700001902163700001902182700002402201700002302225856012302248 2016 eng d a1054-252300aSynthesis, biological evaluation and molecular docking of novel coumarin incorporated triazoles as antitubercular, antioxidant and antimicrobial agents0 aSynthesis biological evaluation and molecular docking of novel c a233 SPRING STREET, 6TH FLOOR, NEW YORK, NY 10013 USAbSPRINGER BIRKHAUSERcAPR a790-8040 v253 a

A series of new coumarin-based 1,2,3-triazole derivatives were designed, synthesized and evaluated for their antitubercular activity in vitro against Mycobacterium tuberculosis H37Ra, antioxidant activity by DPPH radical scavenging assay, antimicrobial activity in vitro against three gram-positive bacteria (Staphylococcus aureus, Micrococcus luteus and Bacillus cereus) and three gram-negative bacteria (Escherichia coli, Pseudomonas fluorescens and Flavobacterium devorans as well as three fungi (Aspergillus niger, Penicillium chrysogenum and Curvularia lunata). The bioactive assay showed that some synthesized coumarin triazoles displayed comparable or even better antitubercular, antioxidant, antibacterial and antifungal efficacy in comparison with reference drugs. Furthermore, docking study has been performed against DprE1 enzyme of M. tuberculosis that showed good binding interactions. Moreover, the synthesized compounds were also analyzed for ADME properties and showed potential to build up as good oral drug candidates. New coumarin-based 1,2,3-triazole derivatives were designed, synthesized and evaluated for their antitubercular, antioxidant, antibacterial and antifungal activity. Some of the coumarin-based triazole derivatives displayed comparable or even better efficacy in comparison with reference drugs. Molecular docking study has been performed against DprE1 enzyme of Mycobacterium tuberculosis showed good binding interactions. [GRAPHICS] .

10a110a210a3-Triazole10aADME prediction10aAntimicrobial10aAntioxidant10aAntitubercular10aClick chemistry10aDocking study1 aShaikh, Mubarak, H.1 aSubhedar, Dnyaneshwar, D.1 aShingate, Bapurao, B.1 aKhan, Firoz, A. Kalam1 aSangshetti, Jaiprakash, N.1 aKhedkar, Vijay, M.1 aNawale, Laxman1 aSarkar, Dhiman1 aNavale, Govinda, R.1 aShinde, Sandip, S. uhttps://library.ncl.res.in/content/synthesis-biological-evaluation-and-molecular-docking-novel-coumarin-incorporated-102019nas a2200265 4500008004100000022001400041245015300055210006900208260007400277300001400351490000700365520100300372653002201375653001601397653001801413653002101431653003601452100002401488700002201512700002301534700002101557700001901578700002601597856013001623 2016 eng d a0922-616800aSynthesis, biological evaluation and molecular docking studies of N-acylheteroaryl hydrazone derivatives as antioxidant and anti-inflammatory agents0 aSynthesis biological evaluation and molecular docking studies of aVAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDSbSPRINGERcMAR a2707-27290 v423 a

In search of new therapeutics with greater potency, three new series of 3-methyl-1-phenyl-1H-thieno[2,3-c]pyrazole-5-carbohydrazide derivatives have been synthesized and evaluated for their in vitro antioxidant and anti-inflammatory activities. The hydrazones bearing a core pyrazole, chromone and tetrazolo[1,5-a]quinoline scaffold showed promising activities. Interestingly, compounds 3a (EC50 = 06.00 +/- A 2.36) and 5c (EC50 = 07.21 +/- A 0.67) showed the most potent antioxidant activity, while compounds 3a (EC50 = 10.25 +/- A 1.08), 7b (EC50 = 10.50 +/- A 0.99) and 7c (EC50 = 11.18 +/- A 0.15) showed significant anti-inflammatory activity. Furthermore, molecular docking studies also revealed a significant correlation between the binding score and biological activity for these compounds to describe the molecular basis for the structure activity relationship (SAR) results. As these compounds are good cyclooxygenase inhibitors, isoenzyme inhibitory potency studies are warranted.

10aAnti-inflammatory10aAntioxidant10aDocking study10aN-Acylhydrazones10aStructure-activity relationship1 aMahajan, Pravin, S.1 aNikam, Mukesh, D.1 aKhedkar, Vijay, M.1 aJha, Prakash, C.1 aSarkar, Dhiman1 aGill, Charansingh, H. uhttps://library.ncl.res.in/content/synthesis-biological-evaluation-and-molecular-docking-studies-n-acylheteroaryl-hydrazone-102543nas a2200325 4500008004100000022001400041245016900055210006900224260010700293300001400400490000700414520138800421653000601809653000601815653001701821653002801838653001701866653001101883653002201894653001301916100001801929700001901947700001801966700001901984700001902003700002302022700002102045700001902066856013202085 2016 eng d a0960-894X00aSynthesis, biological evaluation and molecular docking study of some novel indole and pyridine based 1,3,4-oxadiazole derivatives as potential antitubercular agents0 aSynthesis biological evaluation and molecular docking study of s aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcAPR  a1776-17830 v263 a

A series of indole and pyridine based 1,3,4-oxadiazole derivatives 5a-t were synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG both in active and dormant state. Compounds 5b, 5e, 5g and 5q exhibited very good antitubercular activity. All the newly synthesized compounds 5a-t were further evaluated for antiproliferative activity against HeLa, A549 and PANC-1 cell lines using modified MTT assay and found to be noncytotoxic. On the basis of cytotoxicity and MIC values against Mycobacterium bovis BCG, selectivity index (SI) of most active compounds 5b, 5e, 5g and 5q was calculated (SI = GI(50)/MIC) in active and dormant state. Compounds 5b, 5e and 5g demonstrated SI values >= 10 against all three cell lines and were found to safe for advance screening. Compounds 5a-t were further screened for their antibacterial activity against four bacteria strains to assess their selectivity towards MTB. In addition, the molecular docking studies revealed the binding modes of these compounds in active site of enoyl reductase (InhA), which in turn helped to establish a structural basis of inhibition of mycobacteria. The potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for further optimization. (C) 2016 Elsevier Ltd. All rights reserved.

10a110a310a4-Oxadiazole10aAntitubercular activity10aCytotoxicity10aIndole10aMolecular docking10aPyridine1 aDesai, N., C.1 aSomani, Hardik1 aTrivedi, Amit1 aBhatt, Kandarp1 aNawale, Laxman1 aKhedkar, Vijay, M.1 aJha, Prakash, C.1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/synthesis-biological-evaluation-and-molecular-docking-study-some-novel-indole-and-pyridine-002253nas a2200181 4500008004100000022001400041245014600055210006900201260009100270300002900361490000700390520147700397100001601874700001901890700001901909700001901928856012401947 2016 eng d a1932-620300aTwo chitotriose-specific lectins show anti-angiogenesis, induces caspase-9-mediated apoptosis and early arrest of pancreatic tumor cell cycle0 aTwo chitotriosespecific lectins show antiangiogenesis induces ca a1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USAbPUBLIC LIBRARY SCIENCEcJAN aArticle Number: e01461100 v113 a

The antiproliferative activity of two chito-specific agglutinins purified from Benincasa hispida (BhL) and Datura innoxia (DiL9) of different plant family origin was investigated on various cancer cell lines. Both lectins showed chitotriose specificity, by inhibiting lectin hemagglutinating activity. On further studies, it was revealed that these agglutinins caused remarkable concentration-dependent antiproliferative effect on human pancreatic cancerous cells but not on the normal human umbilical vein endothelial cells even at higher doses determined using MTT assay. The GI(50) values were approximately 8.4 mu g ml(-1) (0.247 mu M) and 142 mu g ml(-1) (14.8 mu M) for BhL and DiL9, respectively, against PANC-1 cells. The growth inhibitory effect of these lectins on pancreatic cancer cells were shown to be a consequence of lectin cell surface binding and triggering G(0)/G(1) arrest, mitochondrial membrane depolarization, sustained increase of the intracellular calcium release and the apoptotic signal is amplified by activation of caspases executing cell death. Interestingly, these lectins also showed anti-angiogenic activity by disrupting the endothelial tubulogenesis. Therefore, we report for the first time two chito-specific lectins specifically binding to tumor glycans; they can be considered to be a class of molecules with antitumor activity against pancreatic cancer cells mediated through caspase dependent mitochondrial apoptotic pathway.

1 aSingh, Ruby1 aNawale, Laxman1 aSarkar, Dhiman1 aSuresh, C., G. uhttps://library.ncl.res.in/content/two-chitotriose-specific-lectins-show-anti-angiogenesis-induces-caspase-9-mediated-102007nas a2200181 4500008004100000245012400041210006900165260000800234300001300242490000800255520133400263100001901597700001701616700002301633700001901656700002101675856012901696 2017 eng d00aAnti-proliferative effect of novel primary cetyl alcohol derived sophorolipids against human cervical cancer cells HeLa0 aAntiproliferative effect of novel primary cetyl alcohol derived  cAPR ae01742410 v12 3 aSophorolipids (SLs) are glycolipid biosurfactants that have been shown to display anticancer activity. In the present study, we report anti-proliferative studies on purified forms of novel SLs synthesized using cetyl alcohol as the substrate (referred as SLCA) and their anticancer mechanism in human cervical cancer cells. Antiproliferative effect of column purified SLCA fractions (A, B, C, D, E and F) was examined in panel of human cancer cell lines as well as primary cells. Among these fractions, SLCA B and C significantly inhibited the survival of HeLa and HCT 116 cells without affecting the viability of normal human umbilical vein endothelial cells (HUVEC). The two fractions were identified as cetyl alcohol sophorolipids with non-hydroxylated tail differing in the degree of acetylation on sophorose head group. At an IC50 concentration SLCA B (16.32 mu g ml(-1)) and SLCA C (14.14 mu g ml(-1)) blocked the cell cycle progression of HeLa cells at G1/S phase in time-dependent manner. Moreover, SLCA B and SLCA C induced apoptosis in HeLa cells through an increase in intracellular Ca2+ leading to depolarization of mitochondrial membrane potential and increase in the caspase-3, -8 and -9 activity. All these findings suggest that these SLCAs could be explored for their chemopreventive potential in cervical cancer.1 aNawale, Laxman1 aDubey, Parul1 aChaudhari, Bhushan1 aSarkar, Dhiman1 aPrabhune, Asmita uhttps://library.ncl.res.in/content/anti-proliferative-effect-novel-primary-cetyl-alcohol-derived-sophorolipids-against-human02356nas a2200157 4500008004100000245012300041210006900164260000800233490000600241520173700247100001701984700002302001700001902024700002502043856013002068 2017 eng d00aCarboxymethyl cellulose-grafted mesoporous silica hybrid nanogels for enhanced cellular uptake and release of curcumin0 aCarboxymethyl cellulosegrafted mesoporous silica hybrid nanogels cFEB0 v33 a

Mesoporous silica nanoparticles (MSNs) with ordered pore structure have beensynthesized and used as carriers for the anticancer drug curcumin. MSNs were functionalizedwith amine groups and further attached with carboxymethyl cellulose (CMC) using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) coupling chemistry, which increased the hydrophilicityand biocompatibility of MSNs. The functionalized MSNs (MSN-NH2and MSN-CMC) werecharacterized using Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM),Dynamic Light Scattering (DLS), N2adsorption, X-Ray Diffraction (XRD), Thermo GravimetricAnalysis (TGA) and Fourier Transform Infrared Spectroscopy (FT-IR). Thein vitrorelease of curcuminfrom the –NH2and CMC functionalized MSNs (MSN-cur-NH2and MSN-cur-CMC) was performedin 0.5% aqueous solution of sodium lauryl sulphate (SLS). The effect of CMC functionalization ofMSNs towards cellular uptake was studied in the human breast cancer cell line MDA-MB-231 andwas compared with that of MSN-NH2and free curcumin (cur). Both MSN-NH2and MSN-CMCshowed good biocompatibility with the breast cancer cell line. The MTT assay study revealedthat curcumin-loaded MSN-cur-CMC showed better uptake as compared to curcumin-loadedMSN-cur-NH2. Free curcumin was used as a control and was shown to have much less internalizationas compared to the curcumin-loaded functionalized MSNs due to poor bioavailability. Fluorescencemicroscopy was used to localize the fluorescent drug curcumin inside the cells. The workdemonstrates that CMC-functionalized MSNs can be used as potential carriers for loading and releaseof hydrophobic drugs that otherwise cannot be used effectively in their free form for cancer therapy.

1 aTiwari, Neha1 aNawale, Laxman, U.1 aSarkar, Dhiman1 aBadiger, Manohar, V. uhttps://library.ncl.res.in/content/carboxymethyl-cellulose-grafted-mesoporous-silica-hybrid-nanogels-enhanced-cellular-uptake00768nas a2200193 4500008004100000245016500041210006900206260000800275300001400283490000700297100002300304700002200327700002000349700002800369700001900397700002000416700001900436856011900455 2017 eng d00aClick-chemistry-based multicomponent condensation approach for design and synthesis of spirochromene-tethered 1,2,3-triazoles as potential antitubercular agents0 aClickchemistrybased multicomponent condensation approach for des cOCT a5675-56900 v431 aChavan, Pramod, V.1 aPandit, Kapil, S.1 aDesai, Uday, V.1 aWadgaonkar, Prakash, P.1 aNawale, Laxman1 aBhansali, Sujit1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/click-chemistry-based-multicomponent-condensation-approach-design-and-synthesis02168nas a2200205 4500008004100000245010200041210006900143260000800212490000800220520142500228100002201653700002301675700001701698700002401715700002501739700001901764700002401783700002501807856013001832 2017 eng d00aHybrids of thienopyrimidinones and thiouracils as anti-tubercular agents: SAR and docking studies0 aHybrids of thienopyrimidinones and thiouracils as antitubercular cJAN0 v1273 a

A number of hybrid molecules containing thienopyrimidinones and thiouracil moieties were designed, synthesized and tested against Mycobacterium tuberculosis H37Ra wherein it was observed that the compounds 11-1514 exhibited antitubercular activity in vitro (MIC 7.6–19.1 μg/ml, 12–35 μM) against dormant stage while compound 15 exhibited antitubercular activity in vitro against dormant (MIC 23.4 μg/ml, 41 μM) as well as active (MIC 25.4 μg/ml, 45 μM) stage. Structural modifications of compound 15 were carried out to study the structure-activity relationship and it was observed that compound 18 exhibited antitubercular activity comparable to compound 15. Cytotoxicity studies revealed that these molecules were non-toxic. The docking study of compound 15 showed that there was binding with the active site of mycobacterial pantothenate synthetase. Further docking studies led to the synthesis of the compounds 16 and 17 and the antitubercular activity screening results showed that these compounds have significant antitubercular activity. The compounds 15-18 (MIC 11–29 μg/ml, 19–51 μM) can be used as starting points for further optimization. The synthetic strategies used in the present work have potential to prepare a large number of compounds for further refinement of structures and the present results will be very useful in the development of a new class of antimycobacterial agents.

1 aPisal, Mahesh, M.1 aNawale, Laxman, U.1 aPatil, Manoj1 aBhansali, Sujit, G.1 aGajbhiye, Jayant, M.1 aSarkar, Dhiman1 aChavan, Subhash, P.1 aBorate, Hanumant, B. uhttps://library.ncl.res.in/content/hybrids-thienopyrimidinones-and-thiouracils-anti-tubercular-agents-sar-and-docking-studies02700nas a2200349 4500008004100000022001400041245011800055210006900173260000800242490000700250520161600257653000901873653001201882653001801894653002601912653001101938653001801949653001901967653001801986653002202004653002402026653001502050653001202065653002702077100002502104700002002129700002002149700002002169700001902189700001902208856012302227 2017 eng d a0928-493100aMultifunctional inulin tethered silver-graphene quantum dots nanotheranostic module for pancreatic cancer therapy0 aMultifunctional inulin tethered silvergraphene quantum dots nano cSEP0 v783 a

Cancer nanotechnology is an emerging area of cancer diagnosis and therapy. Although considerable progress has been made for targeted drug delivery systems to deliver anticancer agents to particular site of interest, new nanomaterials are frequently being developed and explored for better drug delivery efficiency. In the present work, we have explored a novel nanoformulation based on silver-graphene quantum dots (Ag-GQDs) nanocomposite for its successful implementation for pancreatic cancer specific drug delivery in wistar rats. Carboxymethyl inulin (CMI); a modified variant of natural polysaccharide inulin is tethered with the nanocomposite via carbodiimide coupling to enhance the biocompatibility of nanoformulation. Experiments are performed to investigate the cytotoxicity reduction of silver nanoparticles after inulin tethering as well as anticancer efficacy of the system using 5-Fluorouracil (5-FU) as model drug. SEM, TEM, FT-IR, UV-vis, photoluminescence and anti proliferative assays (MTT) are performed for characterisation of the nanocomposite. Hyaluronic acid (HA) is conjugated as targeting moiety for CD-44 (cancer stem cell marker) to fabricate a complete targeted drug delivery vehicle specific for pancreatic cancer. In the present work two prime objectives were achieved; mitigation the toxicity of silver nanoparticles by inulin coating and it's in vivo application for pancreatic cancer. (C) 2017 Elsevier B.V. All rights reserved.

10aacid10aDextran10aDrug-delivery10agraphene quantum dots10aInulin10aNanocomposite10aNanocomposites10aNanoparticles10aPancreatic Cancer10aSilver nanoparticle10aStrategies10aSystems10aTargeted Drug Delivery1 aJoshi, Preeti, Nigam1 aAgawane, Sachin1 aAgawane, Sachin1 aAgawane, Sachin1 aSarkar, Dhiman1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/multifunctional-inulin-tethered-silver-graphene-quantum-dots-nanotheranostic-module01595nas a2200205 4500008004100000245009600041210006900137260000800206300001400214490000700228520086000235100002701095700002501122700002701147700002301174700002301197700001901220700002101239856012901260 2017 eng d00aNew bithiazolyl hydrazones: novel synthesis, characterization and antitubercular evaluation0 aNew bithiazolyl hydrazones novel synthesis characterization and  cJAN a288–2940 v273 a

New bithiazolyl hydrazones (6a–l) have been first time synthesized by carrying novel one pot cyclocondensation of 5-acyl thiazoles (1a–b), thiosemicarbazide (2) and substituted phenacyl chlorides (4a–f) in freshly prepared ionic liquid, diisopropyl ethyl ammonium acetate (DIPEAc) at room temperature. The newly synthesized compounds have been evaluated for their antitubercular activity and the compounds 3b, 6a, 6b, 6d, 6e, 6f, 6g, and 6l have displayed noticeable antitubercular activity compared to Rifampicin with tolerable cytotoxicity. All these compounds were also screened for their antibacterial activity and found that, compounds 6j and 6k have exhibited a very good antibacterial activity. Molecular docking study has shown better harmony with the evaluation trend shown by these compounds under in vitro antitubercular screening.

1 aBhalerao, Mahendra, B.1 aDhumal, Sambhaji, T.1 aDeshmukh, Amarsinh, R.1 aNawale, Laxman, U.1 aKhedkar, Vijay, M.1 aSarkar, Dhiman1 aMane, Ramrao, A. uhttps://library.ncl.res.in/content/new-bithiazolyl-hydrazones-novel-synthesis-characterization-and-antitubercular-evaluation01624nas a2200193 4500008004100000245013100041210006900172260000800241300001300249490000700262520089200269100003001161700002401191700002301215700001901238700002301257700002601280856012401306 2017 eng d00aQuinolidene based monocarbonyl curcumin analogues as promising antimycobacterial agents: synthesis and molecular docking study0 aQuinolidene based monocarbonyl curcumin analogues as promising a cFEB a 922-9280 v273 a

A series of quinoline incorporated monocarbonyl curcumin analogues was efficiently synthesized using [HDBU][HSO4] as catalyst via Knoevenagel type condensation and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG in dormant state. The analogues 3e, 3h, 4a and 4e exhibited very good antitubercular activity. The antiproliferative activity of the analogues against MCF-7, A549 and HCT-116 cell lines was evaluated using modified MTT assay and these compounds were found to be non-cytotoxic. Molecular docking study has been carried out against M. tuberculosis pantothenate synthetase (MTB PS) enzyme in an effort to enhance the understanding of their action as antitubercular agents. The potency, low cytotoxicity and selectivity of these analogues support them as valid leads for further optimization.

1 aSubhedar, Dnyaneshwar, D.1 aShaikh, Mubarak, H.1 aNawale, Laxman, U.1 aSarkar, Dhiman1 aKhedkar, Vijay, M.1 aShingate, Bapurao, B. uhttps://library.ncl.res.in/content/quinolidene-based-monocarbonyl-curcumin-analogues-promising-antimycobacterial-agents01956nas a2200217 4500008004100000245008100041210006900122260000800191300001400199490000800213520120400221100003001425700002401455700002601479700001901505700001901524700002301543700002601566700003101592856011501623 2017 eng d00aQuinolidene-rhodanine conjugates: facile synthesis and biological evaluation0 aQuinolidenerhodanine conjugates facile synthesis and biological  cJAN a385–3990 v1253 a

A series of rhodanine incorporated quinoline derivatives were efficiently synthesized using reusable DBU acetate as ionic liquid and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) (ATCC 25177) and Mycobacterium bovis BCG (ATCC 35743) both in active and dormant state. Compounds 3e, 3f, 3g, 3h and 3i exhibited very good antitubercular activity. The active compounds were studied for cytotoxicity against HUVEC, THP-1, macrophages, A549, PANC-1 and HeLa cell lines using modified MTT assay and were found to be noncytotoxic. Inactivity of all these compounds against Gram positive and Gram negative bacteria indicates their specificity towards the MTB. Further, the synthesized compounds have been screened for their in vitro antifungal activity. In addition, the molecular docking studies revealed the binding modes of these compounds in active site of Zmp1 enzyme, which in turn helped to establish a structural basis of inhibition of mycobacteria. The results of present study clearly indicate the identification of some novel, selective and specific inhibitors against MTB that can be explored further for potential antitubercular drug.

1 aSubhedar, Dnyaneshwar, D.1 aShaikh, Mubarak, H.1 aShingate, Bapurao, B.1 aNawale, Laxman1 aSarkar, Dhiman1 aKhedkar, Vijay, M.1 aKhan, Firoz, A. Kalam1 aSangshetti, Jaiprakash, N. uhttps://library.ncl.res.in/content/quinolidene-rhodanine-conjugates-facile-synthesis-and-biological-evaluation01572nas a2200169 4500008004100000245008700041210006900128260000800197300002400205490000600229520096500235100002101200700002501221700002501246700001901271856011201290 2017 eng d00aSuperoxide generation and its involvement in the growth of mycobacterium smegmatis0 aSuperoxide generation and its involvement in the growth of mycob cJAN aArticle Number: 1050 v83 a

Superoxide generation is inevitable in aerobic organisms, most of which have developed mechanisms to detoxify superoxides. However, its significance has not been clearly understood in mycobacteria. This study demonstrates that NADH oxidase is the major source of superoxide in Mycobacterium smegmatis and elucidates the involvement of superoxide in M. smegmatis growth. The maximum inhibition of superoxide generation was observed in the presence of diphenyleneiodonium chloride (DPI), an NADH oxidase inhibitor, compared to other standard inhibitors. After incubation for 24 h, the number of colony forming units (CFUs) was reduced by 6.8 log10 compared to the untreated culture. The inhibitory effect of DPI on M. smegmatis was reversed when the same culture was supplemented with menadione and pyrogallol, which are superoxide generators. Thus, this study reports the source of superoxide generation and its involvement in the growth of M. smegmatis.

1 aYeware, Amar, M.1 aShurpali, Ketaki, D.1 aAthalye, Meghana, C.1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/superoxide-generation-and-its-involvement-growth-mycobacterium-smegmatis01753nas a2200229 4500008004100000245008300041210006900124260000800193300001200201490000800213520098800221100002301209700002101232700002401253700002501277700002501302700002001327700001901347700001901366700002301385856011501408 2017 eng d00aSynthesis and antimycobacterial screening of new thiazolyl-oxazole derivatives0 aSynthesis and antimycobacterial screening of new thiazolyloxazol cMAY a333-3400 v1323 a

In the present study a series of 4-methyl-2-aryl-5-(2-aryl/benzyl thiazol-4-yl) oxazole (4a-v) have been synthesized and evaluated for their preliminary antitubercular, antimicrobial and cytotoxicity activity. Among all the synthesized compounds, 4v reported comparable activity against dormant M. tuberculosis H37Ra and M. bovis BCG strains with respect to standard drug rifampicin. The active compounds from the antitubercular study were further tested for anti-proliferative activity against HeLa, A549 and PANC-1 cell lines using MU assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Further, the synthesized compounds were found to have potential antibacterial activities with MIC range of 2.1-26.8 mu g/mL. High potency, lower cytotoxicity and promising antimycobacterial activity suggested that these compounds could serve as good leads for further optimisation and development. (C) 2017 Elsevier Masson SAS. All rights reserved.

1 aAbhale, Yogita, K.1 aSasane, Amit, V.1 aChavan, Abhijit, P.1 aShekh, Saddam, Husen1 aDeshmukh, Keshav, K.1 aBhansali, Sujit1 aNawale, Laxman1 aSarkar, Dhiman1 aMhaske, Pravin, C. uhttps://library.ncl.res.in/content/synthesis-and-antimycobacterial-screening-new-thiazolyl-oxazole-derivatives01720nas a2200193 4500008004100000245010400041210006900145260000800214300001200222490000700234520101400241100002501255700002701280700002401307700002401331700001901355700002101374856013101395 2017 eng d00aSynthesis and antitubercular activity of new thiazolidinones with pyrazinyl and thiazolyl scaffolds0 aSynthesis and antitubercular activity of new thiazolidinones wit cJAN a125-1300 v543 a

Emergence of multidrug resistant and extensively drug resistant tuberculosis has prompted to develop new molecular entities to treat the disease. A series of new 4-thiazolidinones with pyrazinyl and thiazolyl scaffolds has been synthesized, and their antitubercular activity is reported. The title 4-thiazolidinones, N-(pyrazinyl substituted thiazoloylamino)-2-aryl-4-thiazolidinones () have been first time prepared using pyrazinamide as a starting material via five successive steps. The purity and the structures of the intermediates (carboethoxythiazole, acid hydrazide, and azomethines) and title thiazolidinones () have been confirmed by TLC and spectral analyses, respectively. An antitubercular screening of the new 4-thiazolidinones has been performed on bacterial strains, Mycobacterium tuberculosis H37Ra and Mycobacterium BCG using the solutions of different concentrations of the compounds () and the screening results are presented. Compound has displayed notable antitubercular activity.

1 aDhumal, Sambhaji, T.1 aDeshmukh, Amarsinh, R.1 aKhillare, Lalit, D.1 aArkile, Manisha, A.1 aSarkar, Dhiman1 aMane, Ramrao, A. uhttps://library.ncl.res.in/content/synthesis-and-antitubercular-activity-new-thiazolidinones-pyrazinyl-and-thiazolyl-scaffolds01659nas a2200205 4500008004100000245012600041210006900167260000800236300001200244490000700256520090900263100001901172700002201191700002301213700002201236700002201258700002401280700001901304856013001323 2017 eng d00aSynthesis and biological evaluation of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione as anti-mycobacterial agents0 aSynthesis and biological evaluation of 124triazole3thione and 13 cJAN a200-2090 v903 aResistance among dormant mycobacteria leading to multi-drug resistant (MDR) and extremely-drug resistant(XDR) tuberculosis is one of the major threats. Hence, a series of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione derivatives (4a-5c) have been synthesised and screened for their anti-tubercular activity against Mycobacterium tuberculosis H37Ra (H37Ra). Thetriazolethiones4b and 4v showed high anti-tubercular activity (both MIC and IC50) against the dormant H37Ra by in vitro and ex vivo. They were shown to have more specificity towards mycobacteria than other gram-negative and gram- positive pathogenic bacteria. The cytotoxicity was almost insignificant up to 100 μg/mL against THP-1, A549 and PANC-1 human cancer cell lines, and solubility was high in aqueous solution, indicating the potential of developing these compounds further as novel therapeutics against tuberculosis infection.1 aSonawane, Amol1 aRode, Navnath, D.1 aNawale, Laxman, U.1 aJoshi, Rohini, R.1 aJoshi, Ramesh, A.1 aLikhite, Anjali, P.1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/synthesis-and-biological-evaluation-124-triazole-3-thione-and-134-oxadiazole-2-thione-anti02332nas a2200241 4500008004100000245010600041210007000147260000800217300001200225490000700237520147700244100002401721700002401745700002901769700002101798700002201819700002601841700002301867700002301890700001901913700002201932856013601954 2017 eng d00aSynthesis and biological evaluation of new fluconazole β-lactam conjugates linked via 1,2,3-triazole0 aSynthesis and biological evaluation of new fluconazole βlactam c cFEB a470-4790 v413 a

Novel 1,2,3-triazole-linked β-lactam–fluconazole conjugates 12(a–l) were designed and synthesized. The compounds showed potent antifungal activity against two pathogenic Candida strains; Candida albicans ATCC 24433 and Candida albicans ATCC 10231 with MIC values in the range of 0.0625–2 μg mL−1. Compounds 12h, 12j and 12k showed promising antifungal activity against all the tested fungal pathogens except C. neoformans ATCC 34554 compared to fluconazole. Compound 12j in which the β-lactam ring was formed using para-anisidine and benzaldehyde was found to be more potent than fluconazole against all the fungal strains with an IC50 value of <0.015 μg mL−1 for Candida albicans (ATCC 24433). Mechanistic studies for active compounds revealed that the antifungal action was due to ergosterol inhibition. Compounds 12h and 12j at a concentration of 0.125 μg mL−1 caused 91.5 and 96.8% ergosterol depletion, respectively, compared to fluconazole which at the same concentration caused 49% ergosterol depletion. The molecular docking study revealed that all the fluconazole β-lactam conjugates 12(a–l) could snugly fit into the active site of lanosterol 14α-demethylase (CYP51) with varying degrees of affinities. As anticipated, the binding energy for compound 12j (−58.961 kcal mol−1) was much smaller than that for fluconazole (−52.92 kcal mol−1). The synthesized compounds have therapeutic potential for the control of candidemia.

1 aDivse, Jaisingh, M.1 aMhaske, Santosh, B.1 aCharolkar, Chaitanya, R.1 aSant, Duhita, G.1 aTupe, Santosh, G.1 aDeshpande, Mukund, V.1 aKhedkar, Vijay, M.1 aNawale, Laxman, U.1 aSarkar, Dhiman1 aPore, Vandana, S. uhttps://library.ncl.res.in/content/synthesis-and-biological-evaluation-new-fluconazole-%CE%B2-lactam-conjugates-linked-123-triazole01595nas a2200205 4500008004100000245010600041210006900147260000800216300001200224490000700236520087100243100002201114700002501136700002501161700001701186700002401203700001901227700002501246856011801271 2017 eng d00aSynthesis and cell imaging applications of fluorescent mono/di/tri-heterocycl- yl-2,6-dicyanoanilines0 aSynthesis and cell imaging applications of fluorescent monoditri cDEC a979-9880 v273 a

Synthesis of 3,4,5-triheterocyclyl-2,6-dicyanoanilines, starting from heterocyclic aldehydes and 1,2-diheterocycle-substituted ethanones, is described. 2,6-Dicyanoanilines with one or two heterocyclic substituents have also been synthesized. It was found that some of these molecules have selective cell-staining properties useful for cell imaging applications. The compounds 1g, 10f and 11 were found to stain cytoplasm of the cells in contact but not the nucleus while the compound 12 showed affinity to apoptotic cells resulting in blue fluorescence. The cell imaging results with compound 12 were similar to Annexin V-FITC, a known reagent containing recombinant Annexin V conjugated to green-fluorescent FITC dye, used for detection of apoptotic cells. These compounds were found to be non-cytotoxic and have potential application as cell imaging agents.

1 aPisal, Mahesh, M.1 aAnnadate, Ritesh, A.1 aAthalye, Meghana, C.1 aKumar, Dipak1 aChavan, Subhash, P.1 aSarkar, Dhiman1 aBorate, Hanumant, B. uhttps://library.ncl.res.in/content/synthesis-and-cell-imaging-applications-fluorescent-monoditri-heterocycl-yl-2602342nas a2200193 4500008004100000245013600041210006900177260000800246520155600254100002301810700002401833700002501857700002301882700001901905700002801924700002501952700002301977856014802000 2017 eng d00aSynthesis, antimycobacterial screening and molecular docking studies of 4-aryl-4′-methyl-2′-aryl-2,5′-bisthiazole derivatives0 aSynthesis antimycobacterial screening and molecular docking stud cJUL3 aA series of 4-aryl-4′-methyl-2′-aryl-2,5′-bisthia- zole derivatives (5a–o) were synthesized and screened for inhibitory activity against Mycobacterium tuberculosis H37Ra (ATCC 25177) and Mycobacterium bovis BCG (ATCC 35743) strains. Five lead compounds (5e, 5f, 5g, 5h, and 5o) were further confirmed from their dose dependent effect against MTB and Bovine–Calmette–Guerin. The most promising compounds 5f (MIC90: 11.32 μg/mL), 5h (MIC90: 11.59 μg/mL), and 5o (MIC90: 23.64 μg/mL) showed strong antitubercular activity against dormant MTB and BCG as well as almost insignificant cytotoxicity up to 100μg/mL against HeLa, A549, and PANC-1 human cancer cell lines. Further, the synthesized compounds were found to have potential antibacterial activity against Gram-negative bac- teria, Escherichia coli, Pseudomonas flurescence and Gram- positive bacteria, Staphylococcus aureus, Bacillus subtilis. Most of the synthesized compounds showed moderateactivity against fungal strain Candida albicans. Molecular docking studies of these compounds showed significant interactions with crystal structure of the cytochrome P45014α-sterol demethylase (CYP51) PDB ID: 1E9X. Hydrogen bond interactions with SER261 and VAL395 are important interactions for selective inhibition of designed inhibitors. Compounds 5f, 5h, and 5o showed significant interactions with 1E9X. All the experimental results promote us to consider this series as a starting point for the devel- opment of novel, selective and more potent antitubercular agents in the future.1 aAbhale, Yogita, K.1 aShinde, Abhijit, D.1 aDeshmukh, Keshav, K.1 aNawale, Laxman, U.1 aSarkar, Dhiman1 aChoudhari, Prafulla, B.1 aKumbhar, Santosh, S.1 aMhaske, Pravin, C. uhttps://library.ncl.res.in/content/synthesis-antimycobacterial-screening-and-molecular-docking-studies-4-aryl-4%E2%80%B2-methyl-2%E2%80%B2-aryl01938nas a2200217 4500008004100000245016700041210006900208260000800277300001400285490000700299520111000306100002201416700002301438700001901461700002301480700002201503700002401525700001901549700002201568856013001590 2017 eng d00aSynthesis, biological evaluation, and molecular docking studies of novel 3-aryl-5-(alkyl-thio)-1H-1,2,4-triazoles derivatives targeting Mycobacterium tuberculosis0 aSynthesis biological evaluation and molecular docking studies of cDEC a1206-12140 v903 aA small library of new 3-aryl-5-(alkyl-thio)-1H-1,2,4-triazoles was synthesized and screened for the antimycobacterial potency against Mycobacterium tuberculosis H37Ra strain and Mycobacterium bovis BCG both in active and dormant stage. Among the synthesized library, 25 compounds exhibited promising anti-TB activity in the range of IC(50)0.03-5.88g/ml for dormant stage and 20 compounds in the range of 0.03-6.96g/ml for active stage. Their lower toxicity (>100g/ml) and higher selectivity (SI=>10) against all cancer cell lines screened make them interesting compounds with potential antimycobacterial effects. Furthermore, to rationalize the observed biological activity data and to establish a structural basis for inhibition of M.tuberculosis, the molecular docking study was carried out against a potential target MTB CYP121 which revealed a significant correlation between the binding score and biological activity for these compounds. Cytotoxicity and in vivo pharmacokinetic studies suggested that 1,2,4-triazole analogues have an acceptable safety index, in vivo stability and bio-availability.1 aRode, Navnath, D.1 aSonawane, Amol, D.1 aNawale, Laxman1 aKhedkar, Vijay, M.1 aJoshi, Ramesh, A.1 aLikhite, Anjali, P.1 aSarkar, Dhiman1 aJoshi, Rohini, R. uhttps://library.ncl.res.in/content/synthesis-biological-evaluation-and-molecular-docking-studies-novel-3-aryl-5-alkyl-thio-1h01001nas a2200205 4500008004100000245014600041210006900187260000800256490000700264520019900271100002400470700003000494700002600524700003100550700001900581700002400600700001900624700002600643856012600669 2017 eng d00aSynthesis of novel triazole-incorporated isatin derivatives as antifungal, antitubercular, and antioxidant agents and molecular docking study0 aSynthesis of novel triazoleincorporated isatin derivatives as an cJAN0 v543 a

A library of 1,2,3-triazoles efficiently prepared via click chemistry and evaluated for their antifungal, antitubercular, antioxidant, cytotoxicity, molecular docking and ADME prediction.

1 aShaikh, Mubarak, H.1 aSubhedar, Dnyaneshwar, D.1 aKhan, Firoz, A. Kalam1 aSangshetti, Jaiprakash, N.1 aNawale, Laxman1 aArkile, Manisha, A.1 aSarkar, Dhiman1 aShingate, Bapurao, B. uhttps://library.ncl.res.in/content/synthesis-novel-triazole-incorporated-isatin-derivatives-antifungal-antitubercular-and01695nas a2200181 4500008004100000245008700041210006900128260000800197300001200205490000800217520106500225100002301290700001901313700002101332700001901353700002401372856011701396 2018 eng d00aAntibacterial and anti-TB tat-peptidomimetics with improved efficacy and half-life0 aAntibacterial and antiTB tatpeptidomimetics with improved effica cMAY a358-3690 v1523 aNon-natural antimicrobial peptides are ideal as next-generation antibiotics because of their ability to circumvent the problems of drug resistance and in vivo instability. We report novel all-alpha- and alpha,gamma-mixed Tat peptide analogues as potential antibacterial and anti-TB agents. These peptides have broad spectrum antibacterial activities against Gram-positive (MICs 0.61 +/- 0.03 to 1.35 +/- 0.21 mu M with the peptide gamma TatM4) and Gram-negative (MICs 0.71 +/- 0.005 to 1.26 +/- 0.02 M with gamma TatM4) bacteria and are also effective against active and dormant forms of Mycobacterium tuberculosis, including strains that are resistant to rifampicin and isoniazid. The introduction of the non-natural amino acids of the study in the Tat peptide analogues results in increased resistance to degradation by proteolysis, significantly increasing their half-life. The peptides appear to inhibit bacteria by a membrane disruption mechanism, and have only a low cytotoxic effect on mammalian cells. (C) 2018 Elsevier Masson SAS. All rights reserved.1 aBhosle, Govind, S.1 aNawale, Laxman1 aYeware, Amar, M.1 aSarkar, Dhiman1 aFernandes, Moneesha uhttps://library.ncl.res.in/content/antibacterial-and-anti-tb-tat-peptidomimetics-improved-efficacy-and-half-life01323nas a2200205 4500008004100000245010100041210006900142260000800211300001400219490000700233520057900240100002200819700001900841700002400860700001900884700001900903700003500922700002800957856013200985 2018 eng d00aConformational studies of Ant-Pro motif-incorporated cyclic peptides: gramicidin S and avellanin0 aConformational studies of AntPro motifincorporated cyclic peptid cJAN a1197-12010 v423 aThis paper reports conformational changes observed in cyclic bioactive peptides such as gramicidin S and avellanin upon incorporation of a pseudo-beta (C9) Ant-(D)Pro turn motif in their structural frameworks. Solution-state studies suggested that a synthetic gramicidin S analog exhibits a beta-sheet conformation with C9 and C17 intramolecular hydrogen bonding patterns, while its truncated analog disturbs the beta-sheet conformation. Structural details were obtained using a combination of CD studies, X-ray crystal structure studies and nOe-based MD simulation studies.1 aKotmale, Amol, S.1 aSangtani, Ekta1 aGonnade, Rajesh, G.1 aSarkar, Dhiman1 aBurade, Sachin1 aRajamohanan, Pattuparambil, R.1 aSanjayan, Gangadhar, J. uhttps://library.ncl.res.in/content/conformational-studies-ant-pro-motif-incorporated-cyclic-peptides-gramicidin-s-and-avellanin02227nas a2200205 4500008004100000245013300041210006900174260000800243300001400251490000600265520145700271100002301728700002501751700002201776700002001798700002401818700001901842700002801861856013201889 2018 eng d00aDesign and synthesis of 2-amino-thiophene-tethered ureidopenicillin analogs with potentantibacterial and antitubercular activity0 aDesign and synthesis of 2aminothiophenetethered ureidopenicillin cMAR a3122-31260 v33 aUreidopenicillins are a class of penicillins which are antibiotics active against gram-negative bacteria. Herein, we report the synthesis of 2-aminothiophene-tethered ureidopenicillin analogues and their in vitro antibacterial and antitubercular activity. Intriguingly, unlike the reported ureidopenicillins which are active against gram-negative bacteria, the synthesised 2-aminothiophene-tethered ureidopenicillins were significantly active against Gram-positive bacterial strains and showed moderate inhibition towards gram-negative bacterial strains. Among all the analogs, compound 1b containing 2-aminothiophene moiety with minimum inhibitory concentration (MIC): 0.29, 0.32, > 10, > 10 mg/ml for Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa, respectively, showed better anti-bacterial profile as compared to cephalexin and equipotent to ampicillin and amoxicillin on gram-positive bacterial strains. All the derivatives were also screened for anti-TB activity against mycobacterium tuberculosis H37Ra. Among the series, cycloocta-thiophene-tethered cephalexin analog 3c displayed excellent antitubercular activity with MIC values 0.78 mg/ml. Low cytotoxicity and high selectivity index indicate the efficacy of 3c against mycobacterial infections. The results from present study offer a novel approach to modify the existing drug class of ureidopenicillins to yield antimicrobials with promising utility.1 aWagh, Mahendra, A.1 aBaravkar, Sachin, B.1 aJedhe, Ganesh, S.1 aBorkute, Rachna1 aChoudhari, Amit, S.1 aSarkar, Dhiman1 aSanjayan, Gangadhar, J. uhttps://library.ncl.res.in/content/design-and-synthesis-2-amino-thiophene-tethered-ureidopenicillin-analogs-potentantibacterial02099nas a2200205 4500008004100000022001500041245009900056210006900155260000900224300001700233490000600250520137800256100002601634700002001660700001901680700002701699700001801726700002401744856012501768 2018 eng d a 2365-654900aDesign, synthesis and biological screening of novel 1,3,4-oxadiazoles as antitubercular agents0 aDesign synthesis and biological screening of novel 134oxadiazole c DEC a 13304-133100 v33 aA series of novel 2,5-disubstitued 1,3,4-oxadiazole derivatives bearing 2,2-dimethyl-2,3-dihydrobenzofuran scaffold has been synthesized and screened for antitubercular activity. All the synthesized compounds were characterized by IR, H-1 NMR, C-13-NMR and Mass spectral study. The in vitro antitubercular activity of the synthesized compounds was evaluated against Mycobacterium tuberculosis H37Ra(ATCC 25177) strain. Among the synthesized compounds, four compound displayed good antitubercular activity IC50 values in low micro-gram range (<10 mu g/mL). The antitubercular data suggested that growth inhibition MTB can be imparted by the introduction of a 4- trifluoromethyl phenyl acetylene substituent. Specificity of these compounds was checked by screening them for their anti-bacterial activity against four bacterial strains (Gram-negative strains: E. coli, S. aureus; Gram-positive strains: P. aeruginosa and B. subtilis). None of the compound displayed antibacterial activity against any of the seleted strain. Molecular docking studies were carried out on InhA (FabI/ENR) which shows that the synthesized compounds bind at the catalytic site in a most favourable manner suggesting their potential as anti-mycobacterial agents. The research presented here was found to be adventitious for the development of new therapeutic agents against Mycobacterium infection.1 aTambe, Macchindra, S.1 aChoudhari, Amit1 aSarkar, Dhiman1 aSangshetti, Jaiprakash1 aPatil, Rajesh1 aGholap, Somnath, S. uhttps://library.ncl.res.in/content/design-synthesis-and-biological-screening-novel-134-oxadiazoles-antitubercular-agents02150nas a2200313 4500008004100000022001400041245010200055210006900157260000800226300001300234490000800247520118500255653000601440653000601446653001701452653000601469653002401475653001701499653002701516653001701543653002201560100002001582700002201602700001901624700001901643700002701662700001801689856012901707 2018 eng d a0365-623300aDesign, synthesis, and pharmacological evaluation of fluorinated azoles as anti-tubercular agents0 aDesign synthesis and pharmacological evaluation of fluorinated a cFEB ae17002940 v3513 a

Design, synthesis, and biological screening of 2,2-dimethyl-2,3-dihydrobenzofuran tethered 1,3,4-oxadiazole derivatives as anti-tubercular agents were described. The synthesis of the target compounds was conducted by a series of reaction schemes. All the synthesized compounds were characterized by IR, H-1 NMR, C-13 NMR, and mass spectrometry. The therapeutic potential of the synthesized compounds was confirmed by molecular docking studies. Among the synthesized compounds, 12a, 12c, 12d, 12e, 12g, and 12j were found to be more active against non-replicating than against replicating cultures of Mycobacterium tuberculosis H37Ra ex vivo and in vitro. These compounds exhibit minimum inhibitory concentration (MIC) values in the range of 2.31-23.91g/mL. The cytotoxicity study was conducted against the cell lines THP-1, A549 and PANC-1, and the compounds were observed to be non-toxic to host cells. Molecular docking was conducted with InhA (FabI/ENR) and suggested the antimycobacterial potential of the synthesized compounds. The investigation presented here was found to be adventitious for the development of new therapeutic agents against Mycobacterium infection.

10a110a210a2-dimethyl-210a310a3-dihydrobenzofuran10a4-Oxadiazole10aanti-tubercular agents10aCytotoxicity10aMolecular docking1 aGholap, Somnath1 aTambe, Macchindra1 aNawale, Laxman1 aSarkar, Dhiman1 aSangshetti, Jaiprakash1 aDamale, Manoj uhttps://library.ncl.res.in/content/design-synthesis-and-pharmacological-evaluation-fluorinated-azoles-anti-tubercular-agents02025nas a2200193 4500008004100000245018300041210006900224260000800293300001200301490000800313520126100321100001801582700001701600700002001617700002301637700001901660700002001679856013201699 2018 eng d00aDesign, synthesis, docking studies and biological screening of 2-thiazolyl substituted-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazines as potent HIV-1 reverse transcriptase inhibitors0 aDesign synthesis docking studies and biological screening of 2th cSEP a310-3190 v1573 a1,3-oxazine nucleus and thiazolyl group features prominently in many biologically important natural products as well as bioactive molecules. A series of novel 2-thiazolyl substituted-2,3-dihydro-1H-naphtho [1,2-e][1,3]oxazine derivatives were designed and synthesized based on their structure-activity relationships (SARs) from 2-naphthol, substituted thiazolyl amines and formalin through ring closure by one-pot three component reaction. These derivatives were first evaluated for their inhibitory effect on HIV-1 Reverse Transcriptase (RT) enzyme activity. Out of 14 compounds, 4 showed potent inhibition of HIV-1 RT activity at significantly low concentration. Docking studies of these molecules revealed their high affinity binding to several amino acids of HIV-1 RT which are less sensitive to point mutations. Furthermore, anti-HIV activity of these molecules was analysed in a CD4(+) T cell-line, which indicates that Therapeutic Index (TI) of some of these compounds is better than Zidovudine and Efavirenz, known HIV-1 RT inhibitors. Taken together, our studies report for the first time some novel naphthoxazine derivatives with significant TI, which is through inhibition of HIV-1 RT activity. (C) 2018 Elsevier Masson SAS. All rights reserved.1 aGawali, Rakhi1 aTrivedi, Jay1 aBhansali, Sujit1 aBhosale, Raghunath1 aSarkar, Dhiman1 aMitra, Debashis uhttps://library.ncl.res.in/content/design-synthesis-docking-studies-and-biological-screening-2-thiazolyl-substituted-23-dihydro02321nas a2200193 4500008004100000022001400041245013500055210006900190260000800259300001600267490000600283520160500289100002301894700002501917700001701942700002001959700001901979856012901998 2018 eng d a2046-206900aMolecular modeling studies and in vitro screening of dihydrorugosaflavonoid and its derivatives against mycobacterium tuberculosis0 aMolecular modeling studies and in vitro screening of dihydrorugo cMAY a10634-106430 v83 a

Novel drug regimens against tuberculosis (TB) are urgently needed and may be developed by targeting essential enzymes of Mtb that sustain the pathogenicity of tuberculosis. In the present investigation, series of compounds (5a-f and 6a-f) based on a naturally occurring rugosaflavonoid moiety were evaluated by in silico molecular modeling studies against -ketoacyl-ACP reductase (MabA) (PDB ID: IUZN) and pantothenate kinase (PanK) (PDB ID: ; 3AF3). Compounds 5a, 5c, 5d, and 6c, which had docking scores of -8.29, -8.36, -8.17 and -7.39 kcal mol(-1), respectively, displayed interactions with MabA that were better than those of isoniazid (-6.81 kcal mol(-1)). Similarly, compounds 5a, 5c, 5d, and 6c, which had docking scores of -7.55, -7.64, -7.40 and -6.7 kcal mol(-1), respectively, displayed interactions with PanK that were comparable to those of isoniazid (-7.64 kcal mol(-1)). Because of their docking scores, these compounds were screened in vitro against Mycobacterium tuberculosis H37Ra (Mtb) using an XRMA protocol. Among the screened compounds, the dihydrorugosaflavonoid derivatives 5a, 5c, and 5d had IC50 values of 12.93, 8.43 and 11.3 g mL(-1), respectively, and exhibited better inhibitory activity than the parent rugosaflavonoid derivatives. The rugosaflavonoid derivative 6c had an IC50 value of 17.57 g mL(-1). The synthesized compounds also displayed inhibitory activity against the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus. The present study will be helpful for the further development of these molecules into antitubercular lead candidates.

1 aPuranik, Ninad, V.1 aSrivastava, Pratibha1 aSwami, Sagar1 aChoudhari, Amit1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/molecular-modeling-studies-and-vitro-screening-dihydrorugosaflavonoid-and-its-derivatives01993nas a2200193 4500008004100000245011500041210006900156260000800225490000700233520126600240100002401506700002601530700001901556700001901575700002601594700002701620700002601647856012601673 2018 eng d00aNovel benzylidenehydrazide-1,2,3-triazole conjugates as antitubercular agents: synthesis and molecular docking0 aNovel benzylidenehydrazide123triazole conjugates as antitubercul cJUL0 v183 aNovel 1,2,3-triazole based benzylidenehydrazide derivatives were synthesized and evaluated for antitubercular activity against Mycobacterium tuberculosis (MTB) H37Ra, M. bovis BCG and cytotoxic activity. Most of the derivatives exhibited promising in vitro potency against MTB characterized by lower MIC values. Among all the synthesized derivatives, compound 6a and 6j were the most active against active and dormant MTB H37Ra, respectively. Compound 6d was significantly active against dormant and active M. bovis BCG. The structure activity relationship has been explored on the basis of anti-tubercular activity data. The active compounds were also tested against THP-1, A549 and Panc-1 cell lines and showed no significant cytotoxicity. Further, the synthesized compounds were found to have potential antioxidant with IC50 range = 11.19-56.64 μg/mL. The molecular docking study of synthesized compounds was performed against DprE1 enzyme of MTB to understand the binding interactions. Moreover, synthesized compounds were also analysed for ADME properties and from all the experimental results, the potency of compounds indicate that, this series considered as starting point for the developement of novel and more potent anti-tubercular agents in future.1 aShaikh, Mubarak, H.1 aSubhedar, Dnyaneshwar1 aNawale, Laxman1 aSarkar, Dhiman1 aKhan, Firoz, A. Kalam1 aSangshetti, Jaiprakash1 aShingate, Bapurao, B. uhttps://library.ncl.res.in/content/novel-benzylidenehydrazide-123-triazole-conjugates-antitubercular-agents-synthesis-and01953nas a2200145 4500008004100000245013800041210006900179260000800248300001000256490000800266520137300274100001701647700001901664856012401683 2018 eng d00aNovel red fluorescence protein based microplate assay for drug screening against dormant mycobacterium tuberculosis by using paraffin0 aNovel red fluorescence protein based microplate assay for drug s cMAY a15-190 v1103 a

The hypoxia model of dormancy is widely used in drug screening programs to identify novel inhibitors against latent Mycobacterium tuberculosis disease. In earlier reported microplate assays, hypoxia was maintained by either sealing the microplate or shifting in an anaerobic chamber to develop dormant phenotype. In these assays, inhibitors were added during inoculation, which mainly represents the active stage inhibitors instead of the dormant ones. Herein, the culture was covered with paraffin to develop hypoxia condition and consequently providing the advantage of adding compounds at any stage during incubation of 96-well plate. The stable expression of the red fluorescent protein in the bacilli under both actively growing as well as dormant conditions also facilitate the reliable estimation of growth and inhibition kinetics of bacilli in medium. Furthermore, S/N ratio and Z' factor of this assay were found to be > 27 and 0.91-0.94 respectively, which confirm the robustness of the protocol. This newly developed drug-screening assay offers an easy, inexpensive, safe and high throughput-screening tool to search novel antitubercular inhibitors against both active and dormant bacilli. The red fluorescent H37Ra strain is a suitable surrogate for the more virulent H37Rv strain, and thus this effort will help in combating latent tuberculosis.

1 aYeware, Amar1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/novel-red-fluorescence-protein-based-microplate-assay-drug-screening-against-dormant01495nas a2200229 4500008004100000022001400041245007200055210006900127260000800196300001400204490000700218520075800225100002200983700002301005700002301028700002101051700002401072700001901096700002601115700002401141856010001165 2018 eng d a1756-891900a Rational design of coumarin derivatives as antituberculosis agents0 aRational design of coumarin derivatives as antituberculosis agen cOCT a2431-24440 v103 aA series of coumarin derivatives was designed as potential antituberculosis agents. Results: The compounds were screened against active and dormant Mycobacterium tuberculosis (Mtb). Compounds 3k and 3n were found to have the most promising activity against replicating MtbH37Rv exhibiting minimum inhibitory concentration of 4.63 and 9.75 mu M respectively. The compounds were also effective against dormant MtbH37Rv exhibiting more potency than the standard drugs, isoniazid and rifampicin. The compounds were found to be non-cytotoxic against human cell lines. Conclusion: This study provides promising antituberculosis agents that are effective against replicating as well as dormant Mtb and can thus act as potential leads for further development. 1 aMali, Hemlata, M.1 aSabale, Sandip, S.1 aDegani, Mariam, S.1 aBorkute, Rachana1 aChoudhari, Amit, S.1 aSarkar, Dhiman1 aKrishna, Vagolu, Siva1 aSriram, Dharmarajan uhttps://library.ncl.res.in/content/rational-design-coumarin-derivatives-antituberculosis-agents01951nas a2200265 4500008004100000022001400041245011500055210006900170260000800239300001400247490000700261520109200268653000601360653000601366653001501372653002701387653002801414653001301442100001801455700002201473700002301495700001901518700001901537856012901556 2018 eng d a0922-616800aSynthesis and biological evaluation of new 2-aryl-4-((4-aryl-1H-1,2,3-triazol-1-yl)methyl)thiazole derivatives0 aSynthesis and biological evaluation of new 2aryl44aryl1H123triaz cFEB a1247-12600 v443 a

A series of 2-aryl-4-((4-aryl-1H-1,2,3-triazol-1-yl)methyl)thiazole derivatives (8a-p) have been synthesized. The structure of the newly synthesized compounds was determined by spectral analysis. The title compounds were screened for their preliminary antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB, ATCC 25177) and Mycobacterium bovis BCG (BCG, ATCC 35743). Further, the synthesized compounds were screened for antimicrobial activity against standard Gram-negative bacteria Escherichia coli (NCIM 2576) and Pseudomonas flurescence (NCIM 2059) and Gram-positive bacteria Staphylococcus aureus (NCIM 2602) and Bacillus subtilis (NCIM 2162). Among all the synthesized compounds, 8a-c, f-h, m exhibited good activity against dormant M. bovis BCG strain. Compounds 8h, j exhibited good activity against all tested bacterial strains. All active compounds were screened for cytotoxicity and found inactive. Their high potency and promising antimycobacterial activity suggest that these compounds could serve as good leads for further optimization and development.

10a110a210a3-Triazole10aantibacterial activity10aAntitubercular activity10aThiazole1 aShinde, Vikas1 aMahulikar, Pramod1 aMhaske, Pravin, C.1 aNawale, Laxman1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/synthesis-and-biological-evaluation-new-2-aryl-4-4-aryl-1h-123-triazol-1-ylmethylthiazole02002nas a2200289 4500008004100000022001200041245013300053210006900186260000800255300000900263490000700272520104300279653000601322653000601328653001601334653002601350653002801376653001701404653002201421100002301443700002401466700001901490700003101509700002301540700002601563856012301589 2018 eng d a922616800aSynthesis and biological evaluation of novel triazole-biscoumarin conjugates as potential antitubercular and anti-oxidant agents0 aSynthesis and biological evaluation of novel triazolebiscoumarin cMAY a1-280 v443 a

The synthesis of a new series of triazole-biscoumarin conjugates by using a molecular hybridization approach is described. The newly synthesized compounds 6a–k were evaluated for their in vitro antitubercular activity against active and dormant Mtb H37Ra and anti-oxidant activity against DPPH radical scavenging. Molecular docking simulations for the antitubercular activity showed that the conjugates 6a–k bind in the pocket of the DprE1 enzyme. Most of the conjugates displayed good antitubercular activity against both the active and dormant Mtb H37Ra strain. The compound 6h displayed very good antitubercular activity against dormant Mtb H37Ra with an IC50 value of 1.44 μg/mL. Most of the synthesized conjugates exhibit excellent anti-oxidant activity with an IC50 of less than the standard BHT. Compound 6b is the most active among all the conjugates with an IC50 value of 08.17 ± 0.11 μg/mL. The molecular docking study shows good agreement between the observed antitubercular activity and the binding affinity.

10a110a210a3-triazoles10aAnti-oxidant activity10aAntitubercular activity10aBiscoumarins10aMolecular docking1 aDanne, Ashruba, B.1 aChoudhari, Amit, S.1 aSarkar, Dhiman1 aSangshetti, Jaiprakash, N.1 aKhedkar, Vijay, M.1 aShingate, Bapurao, B. uhttps://library.ncl.res.in/content/synthesis-and-biological-evaluation-novel-triazole-biscoumarin-conjugates-potential01943nas a2200253 4500008004100000022001200041245016100053210006900214260000900283300000700292490000800299520103300307653004101340653003001381653001701411653001001428100001801438700002101456700002401477700002001501700001901521700001801540856013101558 2018 eng d a974362600aSynthesis and biological evaluation of some bicyclic [2-(2,4-dimethylphenylthio)phenyl] aniline and its amide derivatives as potential antitubercular agents0 aSynthesis and biological evaluation of some bicyclic 224dimethyl cFEB  a220 v1303 a

In the present investigation, a series of bicyclic [2-(2,4-dimethylphenylthio)phenyl] aniline analogues were synthesized and characterized by IR, NMR (1H and 13C) and mass spectra. All newly synthesized 15 compounds were inspected for their in vitro antitubercular activity against Mycobacterium tuberculosis (MTB) H37Ra in both active and dormant state using an established XTT Reduction Menadione assay (XRMA). The titled compounds exhibited minimum inhibitory concentration (MIC90) ranging from 0.05 to >30 (μg/mL). The potent four compounds were further evaluated in THP-1 infection model where they demonstrated significant antitubercular activity. All the ex vivo active were further evaluated for cytotoxic activity against THP-1, MCK7 and HeLa cell lines in order to check selectivity index. All compounds were further screened against four different bacteria to assess their selectivity towards MTB. These derivatives could be considered as a precursor structure for further design of antituberculosis agent.

10a4-dimethylphenylthio)phenyl] aniline10aantituberculosis activity10aCytotoxicity10a[2-(21 aPatil, Yogesh1 aShingare, Ramesh1 aChakraborty, Shakti1 aBorkute, Rachna1 aSarkar, Dhiman1 aMadje, Balaji uhttps://library.ncl.res.in/content/synthesis-and-biological-evaluation-some-bicyclic-2-24-dimethylphenylthiophenyl-aniline-and02623nas a2200277 4500008004100000022001400041245015000055210006900205260000800274300001300282490000800295520166900303653002001972653001901992653002102011653001702032653002202049653002402071100001802095700002102113700002002134700002102154700001902175700002202194856012902216 2018 eng d a0365-623300aSynthesis and biological evaluation of some new tricyclic pyrrolo[3,2-e]tetrazolo[1,5-c]pyrimidine derivatives as potential antitubercular agents0 aSynthesis and biological evaluation of some new tricyclic pyrrol cAUG ae18000400 v3513 a

A series of new tricyclic pyrrolo[3,2-e]tetrazolo[1,5-c]pyrimidines 8a-l were synthesized and characterized by IR, NMR (H-1 and C-13), and mass spectral analysis. The newly synthesized compounds 8a-l were inspected for their in vitro antitubercular activity against Mycobacterium tuberculosis (MTB) H37Ra using an established XTT reduction menadione assay (XRMA). The title compounds exhibited minimum inhibitory concentrations (MIC90) ranging from 0.09 to >30g/mL. Five compounds (8c, 8i-l) were further confirmed for their dose-dependent effect against MTB. These compounds were evaluated in the THP-1 infection model, where 8i (MIC90=0.35g/mL), 8j (MIC90=1.17g/mL), 8k (MIC90=2.38g/mL), and 8l (MIC90=1.17g/mL) demonstrated significant antitubercular activity. All the ex vivo active compounds showed insignificant cytotoxicity against the human cancer cell lines, HeLa, MCF-7, and THP-1. Inactivity of all these compounds against Gram positive and Gram negative bacteria indicates their specificity. Molecular docking studies in the active site of the sterol 14alpha-demethylase (CYP51) enzyme revealed a similar binding mode to the native ligand in the crystal structure, thereby helping to understand the ligand-protein interactions and to establish a structural basis for inhibition of MTB. The results suggest novel pharmacophores as selective and specific inhibitors against MTB that can be explored further to synthesize lead compounds against tuberculosis. In summary, the results clearly indicate the identification of some novel, selective, and specific inhibitors against MTB that can be explored further for potential antitubercular drugs.

10a2-e]tetrazolo[110a5-c]pyrimidine10aAntituberculosis10aCytotoxicity10aMolecular docking10atricyclic pyrrolo[31 aPatil, Yogesh1 aShingare, Ramesh1 aChoudhari, Amit1 aBorkute, Rachana1 aSarkar, Dhiman1 aMadje, Balaji, R. uhttps://library.ncl.res.in/content/synthesis-and-biological-evaluation-some-new-tricyclic-pyrrolo32-etetrazolo15-cpyrimidine01948nas a2200265 4500008004100000022001100041245013300052210006900185260000800254300001200262490000700274520102200281653002701303653003001330653002601360100001801386700001801404700001901422700002801441700001901469700002001488700002301508700001901531856013201550 2018 eng d a39791100aSynthesis, biological evaluation, and molecular docking study of pyridine clubbed 1,3,4-oxadiazoles as potential antituberculars0 aSynthesis biological evaluation and molecular docking study of p cJAN a524-5400 v483 a

A series of pyridine clubbed 1,3,4-oxadiazole derivatives were efficiently synthesized, characterized by standard spectral techniques and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis (MTB) H37Ra and Mycobacterium bovis BCG in active and dormant state using an established methods. Compounds 5a, 5m, and 5t were identified as the most active compounds against MTB. Molecular docking was performed against MTB enoyl-ACP (CoA) reductase (FabI/ENR/InhA) enzyme to predict the binding modes and affinity. The theoretical predictions from molecular docking could establish a link between the observed biological activity and the binding affinity shedding light into specific bonded and non-bonded interactions influencing the activity. The active compounds were studied for cytotoxicity against three cell lines and were found to be non-cytotoxic. Specificity of these compounds was checked by screening them for their antibacterial activity against four bacterial strains.

10aantibacterial activity10aantituberculosis activity10acytotoxicity activity1 aDesai, N., C.1 aTrivedi, Amit1 aSomani, Hardik1 aJadeja, Krunalsingh, A.1 aVaja, Darshita1 aNawale, Laxaman1 aKhedkar, Vijay, M.1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/synthesis-biological-evaluation-and-molecular-docking-study-pyridine-clubbed-134-oxadiazoles01848nas a2200205 4500008004100000022001400041245011900055210006900174260000900243300001400252490000600266520110100272100002301373700002401396700002401420700001901444700002301463700002601486856013001512 2018 eng d a2040-250300aTriazole-diindolylmethane conjugates as new antitubercular agents: synthesis, bioevaluation, and molecular docking0 aTriazolediindolylmethane conjugates as new antitubercular agents cJUL  a1114-11300 v93 a

We describe the synthesis of novel triazole-incorporated diindolylmethanes (DIMs) using a molecular hybridization approach. The in vitro antitubercular activity of the DIMs against Mycobacterium tuberculosis H37Ra (ATCC 25177) was tested in the active and dormant state. Among all the synthesized conjugates, the compounds 6b, 6f, 6l, 6n, 6q, 6r, and 6s displayed good antitubercular activity against both the active and dormant Mtb H37Ra strain. The compound 6l exhibited good antitubercular activity against dormant Mtb H37Ra with an IC50 value of 1 g mL(-1) and IC90 (MIC) value of 3 g mL(-1). The compounds 6b, 6l, and 6r displayed good antitubercular activity against active Mtb H37Ra with IC50 values of 2.19, 1.52, and 0.22 g mL(-1), respectively. The compounds 6b, 6h, 6l, and 6s displayed more than 70% inhibition against the Gram-positive Bacillus subtilus strain at 3 g mL(-1). The molecular docking study showed the binding modes of the titled compounds in the active site of the DprE1 enzyme and assisted with elucidating a structural basis for the inhibition of Mycobacteria.

1 aDanne, Ashruba, B.1 aChoudhari, Amit, S.1 aChakraborty, Shakti1 aSarkar, Dhiman1 aKhedkar, Vijay, M.1 aShingate, Bapurao, B. uhttps://library.ncl.res.in/content/triazole-diindolylmethane-conjugates-new-antitubercular-agents-synthesis-bioevaluation-and02684nas a2200301 4500008004100000022001400041245015500055210006900210260000800279300002100287490000700308520162000315653001601935653003001951653001601981653002301997653002002020653002202040653002102062100002402083700002202107700002002129700002202149700003102171700001902202700003002221856013102251 2018 eng d a1420-304900aUltrasound assisted synthesis of 4-(Benzyloxy)-N-(3-chloro-2-(substitutedphenyl)-4-oxoazetidin-1-yl) benzamide as challenging anti-tubercular scaffold0 aUltrasound assisted synthesis of 4BenzyloxyN3chloro2substitutedp cAUG aArticle No: 19450 v233 a

A series of ten novel derivatives of 4-(benzyloxy)-N-(3-chloro-2-(substituted phenyl)-4-oxoazetidin-1-yl) benzamide 6a-j were synthesized in good yield from the key compound 4-(benzyloxy)-N-(substituted benzylidene) benzo hydrazide, called Schiff `s bases 5a-j, by Staudinger reaction ([2 + 2] ketene-imine cycloaddition reaction) with chloro acetyl chloride in the presence of catalyst tri ethylamine and solvent dimethyl formamide (DMF), by using ultra-sonication as one of the green chemistry tools. All the synthesised compounds were evaluated for in vitro anti-tubercular activity against Mycobacterium tuberculosis (MTB) and most of them showed promising activity with an IC50 value of less than 1 mu g/mL. To establish the safety, all the synthesized compounds were further tested for cytotoxicity against the human cancer cell line HeLa and all 6a-j compounds were found to be non-cytotoxic in nature. The molecular docking study was carried out with essential enzyme InhA (FabI/ENR) of Mycobacterium responsible for cell wall synthesis which suggests that 6a and 6e are the most active derivatives of the series. The theoretical evaluation of cell permeability based on Lipinski's rule of five has helped to rationalize the biological results and hence the synthesized azetidinone derivatives 6a-j were also analyzed for physicochemical evaluation that is, absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties and the results showed that all the derivatives could comply with essential features required for a potential lead in the anti-tubercular drug discovery process.

10aADMET study10aanti-tubercular screening10aazetidinone10acytotoxicity study10agreen chemistry10aMolecular docking10aultra-sonication1 aNimbalkar, Urja, D.1 aSeijas, Julio, A.1 aBorkute, Rachna1 aDamale, Manoj, G.1 aSangshetti, Jaiprakash, N.1 aSarkar, Dhiman1 aNikalje, Anna, Pratima G. uhttps://library.ncl.res.in/content/ultrasound-assisted-synthesis-4-benzyloxy-n-3-chloro-2-substitutedphenyl-4-oxoazetidin-1-yl02531nas a2200325 4500008004100000022001400041245014900055210006900204260000800273300001200281490000700293520147400300653000601774653000601780653003801786653001501824653002001839653002001859653001701879653002801896653002901924100000501953700000501958700002801963700002301991700002102014700002002035700001902055856013102074 2019 eng d a0045-206800aClick chemistry based multicomponent approach in the synthesis of spirochromenocarbazole tethered 1,2,3-triazoles as potential anticancer agents0 aClick chemistry based multicomponent approach in the synthesis o cAPR a475-4860 v853 a

A series of spirochromenocarbazole tethered 1,2,3-triazoles were synthesized via click chemistry based one-pot, five component reaction between N-propargyl isatins, malononitrile, 4-hydroxycarbazole, aralkyl halides and sodium azide using cellulose supported CuI nanoparticles (Cell-CuI NPs) as the heterogeneous catalyst. Antiproliferative activity of all the synthesized compounds was investigated against panel of cancer cell lines such as MCF-7, MDA-MB-231, HeLa, PANG-1, A-549, and THP-1. Many of the synthesized compounds exhibited good anti-proliferative activity against breast (MCF-7 and MDA-MB-231) and cervical (HeLa) cancer cells with IC50 values less than 10 mu M. In case of MCF-7 cells, among the nine compounds that showed good anti-proliferative activity, compounds 6f and 6j were found to be highly potent (IC50 , = 2.13 mu M and 4.80 mu M, respectively). In case of MDA-MB-231, three compounds (6k, 6j and 6s) showed antiproliferative activity amongst which 6k was the most potent one (IC50 = 3.78 mu M). On the other hand, in cervical cancer HeLa cells, compounds 6b, 6g, 6s and 6u showed excellent antiproliferative activity (IC50 = 4.05, 3.54, 3.83, 3.35 mu M, respectively). All the compounds were found to be nontoxic to the human umbilical vein endothelial cells (HUVECs). AO and EtBr staining and fluorescence microscopy studies of the active compounds (IC50 < 5 mu M) suggested that these compounds induce cell death by apoptosis.

10a110a210a3-Triazolylspirochromenocarbazole10aAnticancer10aApoptotic assay10aClick chemistry10aCytotoxicity10aheterogeneous catalysis10aMulticomponent synthesis1 a1 a1 aWadgaonkar, Prakash, P.1 aTapase, Savita, R.1 aKodam, Kisan, M.1 aChoudhari, Amit1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/click-chemistry-based-multicomponent-approach-synthesis-spirochromenocarbazole-tethered-12302635nas a2200277 4500008004100000022001400041245014100055210006900196260000900265300001400274490000600288520167100294653002101965653002001986653002002006653001502026653002202041100002502063700002302088700002302111700002402134700002002158700001902178700002802197856013202225 2019 eng d a2365-654900aDesign and synthesis of 2-amino-thiophene-proline-conjugates and their anti-tubercular activity against mycobacterium tuberculosis H37Ra0 aDesign and synthesis of 2aminothiopheneprolineconjugates and the cMAR  a2851-28570 v43 a

The emergence of extensively drug resistant tuberculosis (XDRTB) and multi-drug resistant tuberculosis (MDR-TB) has necessitated the development of new drugs with short chemotherapy treatment regime and cost effectiveness. To overcome these challenges, we are reporting the synthesis of a series of 2-amino-thiophene-proline-conjugates which show potent invino and ex-vivo anti-tubercular (anti-TB) activity against mycobacterium tuberculosis (rntb) H37Ra. The synthesis of these 2-amino-thiophene-proline-conjugates was carried out via solution phase peptide coupling reactions using methyl-2aminothiophene-3-carboxylate 8 as an intermediate obtained by modified gewald reaction. Intermediate 8 was coupled with different amino acids to obtain dipeptides 3, 4, 5, 6a and 7. Priliminary anti-TB assay data encoureaged us to synthesize modified proline derivatives 6b-6k via formation of a benzoxazinone intermediate 16. Most of these conjugates are active against mtb H37Ra in both active (A) and dormant (D) strains. They are also active against drug resistant mtb H37Ra strains. A trifluoroethyl ester analog, 6i was the most potent among the series [MIC 1 mu g/mL] along with 6f and 6g [MIC 2-6 mu g/mL]. Cytotoxicity studies suggested that, these compounds are less cytotoxic to human cell lines HeLa, MCF-7, HUVEC and hence possess high selectivity index (SI). Docking studies revealed that the binding mode of most active compounds 6i, 6g and 6f is in accordance with their bioactivity studies having docking score 8.969, 8.446 and 7.865, respectively. More- over, in sllico ADME properties suggest that all the compounds possess drug like properties.

10a2-aminothiophene10aAnti-tubercular10adocking studies10aInh A gene10aselectivity index1 aBaravkar, Sachin, B.1 aWagh, Mahendra, A.1 aNawale, Laxman, U.1 aChoudhari, Amit, S.1 aBhansali, Sujit1 aSarkar, Dhiman1 aSanjayan, Gangadhar, J. uhttps://library.ncl.res.in/content/design-and-synthesis-2-amino-thiophene-proline-conjugates-and-their-anti-tubercular-activity01926nas a2200313 4500008004100000022001400041245010800055210006900163260000800232300001200240490000700252520093700259653000601196653000601202653001701208653002001225653001701245653001801262653002201280100002601302700002401328700002501352700002201377700002301399700001901422700002001441700001901461856013201480 2019 eng d a0045-206800aDesign, synthesis and biological evaluation of (E)-5-styryl-1,2,4-oxadiazoles as anti-tubercular agents0 aDesign synthesis and biological evaluation of E5styryl124oxadiaz cMAY a507-5120 v863 a

Cinnamic acid and its derivatives are known for anti-tubercular activity. The present study reports the synthesis of cinnamic acid derivatives via bioisosteric replacement of terminal carboxylic acid with ``oxadiazole''. A series of cinnamic acid derivatives (styryl oxadiazoles) were designed and synthesized in good yields by reaction of substituted cinnamic acids (2, 15a-15s) with amidoximes. The synthesized styryl oxadiazoles were evaluated in vitro for anti-tubercular activity against Mycobacterium tuberculosis (Mtb) H37Ra strain. The structure-activity relationship (SAR) study has identified several compounds with mixed anti-tubercular profiles. The compound 32 displayed potent anti-tubercular activity (IC50= 0.045 mu g/mL). Molecular docking studies on mycobacterial enoyl-ACP reductase enzyme corroborated well with the experimental findings providing a platform for structure based hit-to-lead development.

10a110a210a4-Oxadiazole10aAnti-tubercular10aBioisosteres10aCinnamic acid10aMolecular docking1 aUpare, Abhay, Atmaram1 aGadekar, Pradip, K.1 aSivaramakrishnan, H.1 aNaik, Nishigandha1 aKhedkar, Vijay, M.1 aSarkar, Dhiman1 aChoudhari, Amit1 aRoopan, Mohana uhttps://library.ncl.res.in/content/design-synthesis-and-biological-evaluation-e-5-styryl-124-oxadiazoles-anti-tubercular-agents01700nas a2200169 4500008004100000022001400041245014200055210006900197260000900266300000900275490000600284520105700290100002401347700001901371700001901390856012101409 2019 eng d a2045-232200aEvidence of nitrite acting as a stable and robust inducer of non-cultivability in Mycobacterium tuberculosis with physiological relevance0 aEvidence of nitrite acting as a stable and robust inducer of non cJUN  a92610 v93 a

Tuberculosis (TB) is the ninth leading cause of death worldwide, ranking above human immunodeficiency virus. Latency is the major obstacle in the eradication of this disease. How the physiology of the pathogen changes in transition to the latent stage needs to be understood. The latent bacteria extracted from animal hosts exist in a nonculturable (NC) phase, whereas bacteria extracted from most in vitro models are culture-positive. In the present study, we observed that nitrite, up to a concentration of 5 mM, shows the growth of Mycobacterium tuberculosis (MTB) in liquid media, but this effect starts reversing at higher concentrations. At a concentration of 10 mM, nitrite induces rapid nonculturability of MTB at the aerobic stage. This noncultivable dormancy was confirmed by analyzing the characteristics of NC bacteria. Further differential gene expression analyses clearly supported the formation of a dormancy phenotype. This study will be helpful for the use of this bacillus as a dormancy model in future studies on TB latency.

1 aGample, Suwarna, P.1 aAgrawal, Sonia1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/evidence-nitrite-acting-stable-and-robust-inducer-non-cultivability-mycobacterium01839nas a2200145 4500008004100000245013400041210006900175260000800244490000800252520125400260100001701514700001901531700001901550856012401569 2019 eng d00aHigh content screening assay for identifying inhibitors against active and dormant state intracellular Mycobacterium tuberculosis0 aHigh content screening assay for identifying inhibitors against  cSEP0 v1643 a

The antitubercular drug development pipeline could start with an in vitro investigation of several compounds to examine their effect on active and dormant state Mycobacterium tuberculosis (Mtb). However, in vitro screening of dormant state bacilli cannot provide enough information on the simultaneous effect of a compound on the host. Therefore, we developed a live cell fluorescence based screening protocol by utilizing the high content system for determining the effect of inhibitors against active and dormant state intracellular mycobacteria. THP-1 macrophages infected with an actively growing and hypoxia derived dormant Mtb culture were standardized to develop the screening protocol. The signal to noise ratio and the Z' factor of this assay were found to be 7.5-29 and 0.6-0.8, respectively, which confirm the robustness of the protocol. The protocol was then validated with standard inhibitors. This newly developed drug screening assay offers an easy, safe, image based high content screening tool to search for novel antitubercular inhibitors against both active and dormant state intracellular mycobacteria. Therefore, this assay could fill in the gap between in vitro and in vivo latent tuberculosis drug screening programs.

1 aYeware, Amar1 aAgrawal, Sonia1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/high-content-screening-assay-identifying-inhibitors-against-active-and-dormant-state02855nas a2200337 4500008004100000022001400041245014000055210006900195260000800264300001200272490000700284520166800291653002401959653002801983653003502011653002202046653004102068653002302109100002302132700002202155700003002177700002702207700002302234700002202257700002102279700002602300700002002326700002002346700001902366856013202385 2019 eng d a1573-409900aNon nucleoside reverse transcriptase inhibitors, molecular docking studies and antitubercular activity of thiazolidin-4-one derivatives0 aNon nucleoside reverse transcriptase inhibitors molecular dockin cJAN a433-4440 v153 a

Background: Management of Co-existence of Acquired immunodeficiency syndrome and Tuberculosis has become a global challenge due to the emergence of resistant strains and pill burden. Objective: Hence the aim of the present work was to design and evaluate compounds for their dual activity on HIV-1 and Tuberculosis (TB). Methods: A series of seven, novel Thiazolidin-4-one derivatives were synthesized and evaluated for their anti-HIV and anti-tubercular activity along with Molecular docking studies. All the seven compounds displayed promising activity against the replication of HIV-1 in cell-based assays. The four most active compounds were further evaluated against X4 tropic HIV-1(UG)(070) and R5 tropic HIV-1(vB59) primary isolates. The binding affinity of all the designed compounds for HIV-RT and Mycobacterium tuberculosis Enol Reductase (MTB InhA) was gauged by molecular docking studies which revealed crucial thermodynamic interactions governing their binding. Results: The CC50 values for the test compounds were in the range of, 15.08-34.9 mu g/ml, while the IC50 values were in the range of 16.1-27.13(UG(070); X4) and 12.03-23.64 (VB59; R5) mu g/ml. The control drug Nevirapine (NVP) exhibited CC50 value of 77.13 mu g/ml and IC50 value of 0.03 mu g/ml. Amongst all these compounds, compound number 3 showed significant activity with a TI value of 2.167 and 2.678 against the HIV-1 X4 and the R5 tropic virus respectively. In anti-mycobacterial screening, the compounds proved effective in inhibiting the growth of both log phase and starved MTB cultures. Conclusion: Compound 3 has been found to be active against HIV-1 as well as MTB.

10aanti-HIV-1 activity10aAntitubercular activity10ahuman immunodeficiency virus-110aMolecular docking10aNon nucleoside reverse transcriptase10athiazolidin-4-ones1 aChitre, Trupti, S.1 aPatil, Shital, M.1 aSujalegaonkar, Anagha, G.1 aAsgaonkar, Kalyani, D.1 aKhedkar, Vijay, M.1 aGarud, Dinesh, R.1 aJha, Prakash, C.1 aGaikwad, Sharddha, Y.1 aKulkarni, Smita1 aChoudhari, Amit1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/non-nucleoside-reverse-transcriptase-inhibitors-molecular-docking-studies-and-antitubercular02398nas a2200301 4500008004100000022001400041245011400055210006900169260000800238300001400246490000700260520143100267653002001698653002901718653001901747653001901766653000901785653002701794100002001821700001901841700002101860700001801881700002001899700001901919700002001938700001901958856011901977 2019 eng d a1570-180800aRecursive partitioning analysis and anti-tubercular screening of 3-aminopyrazine-2-carbohydrazide derivatives0 aRecursive partitioning analysis and antitubercular screening of  cAPR a1264-12750 v163 a

Background: Treating tuberculosis is a challenge due to the development of drug resistance. Hence, it is imperative to develop novel leads having high potency and efficacy to curb drug resistance. Methods: The present research work is focused on microwave-assisted synthesis of novel twenty-six 3-amino-N'-benzylidenepyrazine-2-carbohydrazide derivatives (3a-z), where, lyophilization technique was used for isolation of the major intermediate, 3-aminopyrazin-2-carbohydrazide. All synthesized compounds were subjected for anti-tubercular screening against Mycobacterium tuberculosis H37Ra by using XTT Reduction Menadione Assay (XRMA) protocol. Results: Out of 26 synthesized compounds, four N'-substitutedbenzaldehyde-3-amino-pyrazine-2-carbohydrazide derivatives viz. 3i, 3j 3v and 3z showed significant activity against M. tuberculosis H37Ra. The compounds 3i, 3j, 3v and 3z showed 99, 98, 92 and 87 % inhibition respectively as compared to 94% inhibition shown by the standard drug rifampicin. The MIC and IC50 values were in the range of 24.3-110 and 5.9-20.8 mu g/ml respectively. Conclusion: A classification model called Recursive Partitioning (RP) based on binary Quantitative Structure-Activity Relationship (QSAR) was derived for the establishment of structure-activity relationship (SAR). The predictions derived on the basis of RP model were found to be in agreement with anti-tubercular screening data.

10a3-aminopyrazine10aanti-tubercular activity10aCarbohydrazide10alyophilization10aQSAR10arecursive partitioning1 aMiniyar, Pankaj1 aMahajan, Anand1 aAnuse, Dattatray1 aKumar, Ashish1 aBarmade, Mahesh1 aSarkar, Dhiman1 aArkile, Manisha1 aKhedkar, Vijay uhttps://library.ncl.res.in/content/recursive-partitioning-analysis-and-anti-tubercular-screening-3-aminopyrazine-202080nas a2200313 4500008004100000022001400041245012500055210006900180260000800249300001200257490000700269520107300276653000601349653000601355653001501361653002801376653002201404653002701426653001301453100001801466700002201484700002301506700002401529700002001553700002201573700002401595700001901619856012801638 2019 eng d a1054-252300aSynthesis and antimycobacterial evaluation of new 5-(1-benzyl-1H-1,2,3-triazol-4-yl)-4-methyl-2-arylthiazole derivatives0 aSynthesis and antimycobacterial evaluation of new 51benzyl1H123t cJUN a805-8190 v283 a

A new series of 5-(1-benzyl-1H-1,2,3-triazol-4-yl)-4-methyl-2-arylthiazole derivatives, 6a-w have been synthesized by click reaction of substituted benzylazide, 5a-d with 5-ethynyl-4-methyl-2-substituted phenylthiazole, 4a-f. The starting compounds 4-ethynyl-2-substituted phenylthiazole (4a-f) were synthesized from the corresponding thiazole aldehyde by using the Ohira-Bestmann reagent. The structure of the synthesized compounds was determined by spectral analysis. All the synthesized compounds were screened for their preliminary antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB, ATCC 25177). Most of the synthesized compounds reported good activity against M. tuberculosis H37Ra strain with IC50 range of 0.58-8.23 mu g/mL. Compounds 6g and 6k reported good antitubercular activity with MIC90 values of 4.71 and 2.22 mu g/mL, respectively. Potential antimycobacterial activity suggested that these compounds could serve as good lead compounds for further optimization and development of a newer antitubercular candidate. [GRAPHICS] .

10a110a210a3-Triazole10aAntitubercular activity10aMolecular docking10aOhira-Bestmann reagent10aThiazole1 aShinde, Vikas1 aMahulikar, Pramod1 aMhaske, Pravin, C.1 aChakraborty, Shakti1 aChoudhari, Amit1 aPhalle, Siddharth1 aChoudhari, Prafulla1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/synthesis-and-antimycobacterial-evaluation-new-5-1-benzyl-1h-123-triazol-4-yl-4-methyl-201775nas a2200277 4500008004100000245014700041210006900188260000800257300001200265490000800277520079400285100002201079700002601101700002001127700002401147700002201171700002301193700002001216700002101236700001701257700001901274700002401293700003001317700002201347856012801369 2019 eng d00aSynthesis and biological evaluation of 2,4,5-trisubstituted thiazoles as antituberculosis agents effective against drug-resistant tuberculosis0 aSynthesis and biological evaluation of 245trisubstituted thiazol cSEP a315-3280 v1783 a

The dormant and resistant form of Mycobacterium tuberculosis presents a challenge in developing new anti-tubercular drugs. Herein, we report the synthesis and evaluation of trisubstituted thiazoles as antituberculosis agents. The SAR study has identified a requirement of hydrophobic substituent at C2, ester functionality at C4, and various groups with hydrogen bond acceptor character at C5 of thiazole scaffold. This has led to the identification of 13h and 13p as lead compounds. These compounds inhibited the dormant Mycobacterium tuberculosis H37Ra strain and M. tuberculosis H37Rv selectively. Importantly, 13h and 13p were non-toxic to CHO cells. The 13p showed activity against multidrug-resistant tuberculosis isolates. (C) 2019 Elsevier Masson SAS. All rights reserved.

1 aKarale, Uttam, B.1 aKrishna, Vagolu, Siva1 aKrishna, Vamshi1 aChoudhari, Amit, S.1 aShukla, Manjulika1 aGaikwad, Vikas, R.1 aMahizhaveni, B.1 aChopra, Sidharth1 aMisra, Sunil1 aSarkar, Dhiman1 aSriram, Dharmarajan1 aDusthackeer, V., N. Azger1 aRode, Haridas, B. uhttps://library.ncl.res.in/content/synthesis-and-biological-evaluation-245-trisubstituted-thiazoles-antituberculosis-agents02021nas a2200169 4500008004100000022001400041245012100055210006900176260000800245520137700253100001801630700002301648700001901671700001901690700002201709856012001731 2019 eng d a0022-152X00aSynthesis and biological evaluation of new 4-(4-(1-benzyl-1H-1,2,3-triazol-4-yl)phenyl)-2-phenylthiazole derivatives0 aSynthesis and biological evaluation of new 441benzyl1H123triazol cSEP3 a

A novel series of 4-(4-(1-benzyl-1H-1,2,3-triazol-4-yl)phenyl)-2-substitutedthiazole derivatives (8a-l) have been synthesized by [3 + 2] cycloaddition reaction of 4-(4-ethynylphenyl)-2-substitutedthiazole with substituted benzyl azide in aqueous DMF. Starting compounds 4-(4-ethynylphenyl)-2-substitutedthiazole (6a-d) were synthesized by reaction of 4-(2-substitutedthiazol-4-yl)benzaldehyde with Ohira-Bestmann reagent in methanol. The structures of these novel triazole-thiazole clubbed derivatives were confirmed by the spectral analysis. The title compounds (8a-l) were tested for antimycobacterial activity against Mycobacterium tuberculosis H37Ra active and dormant (MTB, ATCC 25177) and antimicrobial activity against standard Gram-positive bacteria, Staphylococcus aureus (NCIM 2602) and Bacillus subtilis (NCIM 2162), and Gram-negative bacteria, Escherichia coli (NCIM 2576) and Pseudomonas flurescence (NCIM 2059). Compounds 8a, 8b, 8c, and 8h reported good activity against B subtilis, compounds 8a, 8b, and 8c showed good activity against S aureus, and compound 8b showed good activity against dormant M tuberculosis H37Rv strain. Compounds 8b and 8c found more potent against Gram positive and dormant M tuberculosis H37Rv strains. These novel triazole-thiazole clubbed analogues found to be a capable leads for further optimization and development.

1 aShinde, Vikas1 aMhaske, Pravin, C.1 aSingh, Aakriti1 aSarkar, Dhiman1 aMahulikar, Pramod uhttps://library.ncl.res.in/content/synthesis-and-biological-evaluation-new-4-4-1-benzyl-1h-123-triazol-4-ylphenyl-202140nas a2200313 4500008004100000022001400041245017000055210006900225260000800294300001400302490000700316520107600323653000601399653000601405653001701411653002701428653002801455653001701483653002301500653001501523100002401538700002601562700002601588700002001614700002301634700001901657700002201676856012801698 2019 eng d a1054-252300aSynthesis of new 1,3,4-oxadiazole and benzothiazolylthioether derivatives of 4-arylmethylidene-3-substituted-isoxazol-5(4H)-one as potential antimycobacterial agents0 aSynthesis of new 134oxadiazole and benzothiazolylthioether deriv cNOV a1873-18840 v283 a

A new series of 4-[(substituted benzylidene)-3-[(5-(pyridine-4-yl)-1,3,4-oxadiazole-2-ylthio)-methyl]i soxazol-5(4H)-one (6a-g) and 4-(substituted benzylidene)-3-((benzo[d]thiazol-2-ylthio)methyl)isoxazol-5(4H)-one (8a-g) was synthesized. All the synthesized compounds were screened for antitubercular activity against Mycobacterium tuberculosis H37Ra (ATCC 25177) and Mycobacterium bovis BCG (ATCC 35743) and antibacterial activity against Escherichia coli (NCIM 2576), Pseudomonas flurescence (NCIM 2059), Staphylococcus aureus (NCIM 2602), Bacillus subtilis (NCIM 2162). Amongst the synthesized 1,3,4-oxadiazole and benzothiazoyl thioether derivatives, compounds 6b and 8b showed excellent antimycobacterial activity and compounds 6b, 8a, 8b, and 8d showed excellent antibacterial activity against all tested antibacterial strains. The synthesized compounds were further evaluated for their cytotoxic activity against the HCT 116 and HeLa cancer cell lines. The 1,3,4-oxadiazole and benzothiazoyl thioether derivatives 6a-g and 8a-g did not show cytotoxicity.

10a110a310a4-Oxadiazole10aantibacterial activity10aAntitubercular activity10aBenzothiazol10aIsoxazol-5(4H)-one10aThioeteher1 aChavan, Abhijit, P.1 aDeshpande, Rujuta, R.1 aBorade, Nandkumar, A.1 aShinde, Abhijit1 aMhaske, Pravin, C.1 aSarkar, Dhiman1 aBobade, Vivek, D. uhttps://library.ncl.res.in/content/synthesis-new-134-oxadiazole-and-benzothiazolylthioether-derivatives-4-arylmethylidene-301775nas a2200265 4500008004100000022001400041245007300055210006900128260000800197300001400205490000700219520094900226653003101175653001701206653001301223653001401236100002301250700002401273700002601297700002001323700001901343700001901362700002301381856010501404 2019 eng d a0960-894X00aThiazolyl-pyrazole derivatives as potential antimycobacterial agents0 aThiazolylpyrazole derivatives as potential antimycobacterial age cMAY a1199-12020 v293 a

Mycobacterium tuberculosis (Mtb) is an obligate aerobe that is capable of long-term persistence under conditions of low oxygen tension. A series of thiazolyl-pyrazole derivatives (6a-f, 7a-f, 8c, 8e) were screened for antimycobacterial activity against dormant M. tuberculosis H37Ra (D-MTB) and M. bovis BCG (D-BCG). Nine thiazolyl- pyrazole analogs, 6c, 6e, 7a, 7b, 7c, 7e, 7f, 8c and 8e exhibited promissing minimum inhibitory concentration (MIC) values (0.20-28.25 mu g/mL) against D-MTB and D-BCG strains of Mtb. Importantly, six compounds (7a, 7b, 7e, 7f, 8c and 8e) exhibited excellent antimycobacterial activity and low cytotoxicity at the maximum evaluated concentration of > 250 mu g/mL. Finally, the promising antimycobacterial activity and lower cytotoxicity profile suggested that, these compounds could be further subjected for optimization and development as a lead, which could have the potential to treat tuberculosis.

10aantimycobacterial activity10aCytotoxicity10aPyrazole10athiazoles1 aTakate, Sushma, J.1 aShinde, Abhijit, D.1 aKarale, Bhausaheb, K.1 aAkolkar, Hemant1 aNawale, Laxman1 aSarkar, Dhiman1 aMhaske, Pravin, C. uhttps://library.ncl.res.in/content/thiazolyl-pyrazole-derivatives-potential-antimycobacterial-agents02012nas a2200181 4500008004100000022001400041245013800055210006900193260000800262300001300270490000700283520133400290100001701624700002001641700001901661700001901680856013101699 2019 eng d a1932-620300aUsing diphenyleneiodonium to induce a viable but non-culturable phenotype in Mycobacterium tuberculosis and its metabolomics analysis0 aUsing diphenyleneiodonium to induce a viable but nonculturable p cAUG ae02206280 v143 a

Depletion of oxygen levels is a well-accepted model for induction of non-replicating, persistent states in mycobacteria. Increasing the stress levels in mycobacterium bacilli facilitates their entry into a non-cultivable, dormant state. In this study, it was shown that diphenyleneiodonium, an inhibitor of NADH oxidase, induced a viable, but non-culturable state in mycobacteria, having similar features to dormant bacilli, like loss of acid-fastness, upregulation of stress-regulated genes and decreased superoxide levels as compared to actively growing bacilli. Comprehensive, untargeted metabolic profiling also confirmed a decrease in biogenesis of amino acids, NAD, unsaturated fatty acids and nucleotides. Additionally, an increase in the level of lactate, fumarate, succinate and pentose phosphate pathways along with increased mycothiol and sulfate metabolites, similar to dormant bacilli, was observed in the granuloma. These non-cultivable bacilli were resuscitated by supplementation of fetal bovine serum, regaining their culturability in liquid as well as on agar medium. This study focused on the effect of diphenyleneiodonium treatment in causing mycobacteria to rapidly transition from an active state into a viable, but non-cultivable state, and comparing their characteristics with dormant phenotypes.

1 aYeware, Amar1 aGample, Suwarna1 aAgrawal, Sonia1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/using-diphenyleneiodonium-induce-viable-non-culturable-phenotype-mycobacterium-tuberculosis02851nas a2200277 4500008004100000022001400041245013700055210006900192260000800261300001100269490000700280520193000287653002202217653001002239653001502249653002202264653001502286653001002301100002402311700002502335700001902360700002202379700001902401700002202420856013102442 2020 eng d a0946-672X00aAnticancer potential of AgNPs synthesized using acinetobacter sp. and curcuma aromatica against HeLa cell lines: a comparative study0 aAnticancer potential of AgNPs synthesized using acinetobacter sp cDEC a1266300 v623 a

Background: Biogenic nanoparticles are gaining attention due to their low toxicity and numerous biomedical applications. Present study aimed to compare the potential anticancer activity of two biogenic silver nanoparticles (bAgNPs and pAgNPs) against human cervical cancer cell lines (HeLa). Methods: bAgNPs were synthesized using Acinetobacter sp. whereas pAgNPs were synthesized using aqueous root extract of Curcuma aromatica. Effect of these nanoparticles on HeLa cells viability was studied using MTT assay and colony formation assay. Anticancer potential was determined using fluorescence microscopy and flow cytometry studies. Bio-compatibility studies were performed against peripheral blood mononuclear cells (PBMCs). Results: Both the nanoparticles showed 50 % viability of peripheral blood mononuclear cells (PBMCs) when used at high concentration (200 mu g/mL). IC50 for bAgNPs and pAgNPs against HeLa cells were 17.4 and 14 mu g/mL respectively. Colony formation ability of Hela cells was reduced on treatment with both nanoparticles. Acridine orange and ethidium bromide staining demonstrated that bAgNPs were cytostatic whereas pAgNPs were apoptotic. JC-1 dye staining revealed that the mitochondrial membrane potential was affected on treatment with pAgNPs while it remained unchanged on bAgNPs treatment. Flow cytometry confirmed cell cycle arrest in HeLa cells on treatment with nanoparticles further leading to apoptosis in case of pAgNPs. About 77 and 58 % HeLa cells were found in subG1 phase on treatment with bAgNPs and pAgNPs respectively. bAgNPs showed cytostatic effect on HeLa cells arresting the cell growth in subG1 phase, whereas, pAgNPs triggered death of HeLa cells through mitochondrial membrane potential impairment and apoptosis. Conclusion: Overall, bAgNPs and pAgNPs could be safe and showed potential to be used as anticancer nanoantibiotics against human cervical cancer cells.

10aAcinetobacter sp.10aAgNPs10aAnticancer10aCurcuma aromatica10aHeLa cells10aPBMCs1 aNadhe, Shradhda, B.1 aTawre, Madhumita, S.1 aAgrawal, Sonia1 aChopade, Balu, A.1 aSarkar, Dhiman1 aPardesi, Karishma uhttps://library.ncl.res.in/content/anticancer-potential-agnps-synthesized-using-acinetobacter-sp-and-curcuma-aromatica-against02521nas a2200217 4500008004100000022001400041245011100055210006900166260000800235300001200243490000700255520176200262100002302024700001702047700001902064700002502083700002102108700002402129700002102153856012902174 2020 eng d a0343-865100aExploring the pharmacological potentials of biosurfactant derived from planococcus maritimus SAMP MCC 30130 aExploring the pharmacological potentials of biosurfactant derive cMAR a452-4590 v773 a

Therapeutic potential of biosurfactant (BS) has been improved in recent years. Our present study deals with production of BS from Planococcus maritimus SAMP MCC 3013 in a mineral salt medium (MSM) supplemented with glucose (1.5% w/v). Further, BS has been purified and partially characterized as glycolipid type through our previous publication. Current research article aimed to evaluate biological potential of BS against Mycobacterium tuberculosis, Plasmodium falciparum and cancerous cell lines. Planococcus derived glycolipid BS was found to be a promising inhibitor of M. tuberculosis (MTB) H37Ra at IC50 64.11 +/- 1.64 mu g/mL and MIC at 160.8 +/- 1.64 mu g/mL. BS also showed growth inhibition of P. falciparum at EC50 34.56 +/- 0.26 mu M. Additionally, BS also displayed the cytotoxicity against HeLa (IC50 41.41 +/- 4.21 mu g/mL), MCF-7 (IC50 42.79 +/- 6.07 mu g/mL) and HCT (IC50 31.233 +/- 5.08 mu g/mL) cell lines. Molecular docking analysis was carried for the most popular glycolipid type BS namely Rhamnolipid (RHL) aiming to interpret the possible binding interaction for anti-tubercular and anti-cancer activity. This analysis revealed the involvement of RHL binding with enoyl reductase (InhA) of M. tuberculosis. Docking studies of RHL with tubulin directed several hydrophobic and Vander Waal interactions to exhibit anti-cancer potential. The present study will be helpful for further development of marine bioactive molecules for therapeutic applications. Their anti-tubercular, anti-plasmodial and cytotoxic activities make BS molecules as a noteworthy candidate to combat several diseases. To the best of our knowledge, this is the first report on projecting the pharmacological potential of Planococcus derived BS. Graphic

1 aWaghmode, Samadhan1 aSwami, Sagar1 aSarkar, Dhiman1 aSuryavanshi, Mangesh1 aRoachlani, Sneha1 aChoudhari, Prafulla1 aSatpute, Surekha uhttps://library.ncl.res.in/content/exploring-pharmacological-potentials-biosurfactant-derived-planococcus-maritimus-samp-mcc01984nas a2200205 4500008004100000022001400041245013800055210006900193260000800262300001400270490000700284520122800291100002601519700001901545700002001564700002201584700001901606700002301625856013001648 2020 eng d a0022-152X00aSynthesis and antimycobacterial screening of new 4-(4-(1-benzyl-1H-1,2,3-triazol-4-yl)-1-phenyl-1H-pyrazol-3-yl)quinoline derivatives0 aSynthesis and antimycobacterial screening of new 441benzyl1H123t cNOV a3918-39290 v573 a

A new series of 4-(4-(1-benzyl-1H-1,2,3-triazol-4-yl)-1-phenyl-1H-pyrazol-3-yl)quinoline (6a-t) have been synthesized by a click reaction of 4-(4-ethynyl-1-phenyl-1H-pyrazol-3-yl)quinoline (4a-d) with a substituted benzyl azide (5a-e). The starting alkyne derivatives4a-dare obtained from Bestmann-Ohira reaction of 1-phenyl-3-(quinolin-4-yl)-1H-pyrazole-4-carbaldehyde and dimethyl(1-diazo-2-oxopropyl)phosphonate. The newly synthesized compounds are screened againstM. tuberculosisH37Ra dormant and active,Escherichia coli,Pseudomonas fluorescence,Staphylococcus aureusandBacillus subtilisstrains at 30 mu g/mL concentration. Most of the screened compounds showed good to moderate antibacterial activity againstS. aureus,B. subtilis, andMycobacterium tuberculosisH37Ra strains. The synthesized derivatives of quinolinyl-pyrazole-4-carbaldehyde and quinolinyl-pyrazole-4-ethyne reportd good to moderate activity against both strains ofM. tuberculosisH37Ra. Ten derivatives of quinolinyl-pyrazole presented good activity againstB. subtilis. These results suggested that further optimization and development of quinolinyl-pyrazolyl-1,2,3-triazole moeity could serve as lead compounds for antimycobacterial activity.

1 aThakare, Prashant, P.1 aWalunj, Yogesh1 aChavan, Abhijit1 aBobade, Vivek, D.1 aSarkar, Dhiman1 aMhaske, Pravin, C. uhttps://library.ncl.res.in/content/synthesis-and-antimycobacterial-screening-new-4-4-1-benzyl-1h-123-triazol-4-yl-1-phenyl-1h02830nas a2200241 4500008004100000022001400041245016200055210006900217260000800286300001400294490000700308520192300315653002602238653001502264653003902279653003702318653002302355653000902378653002302387100002702410700001902437856013202456 2021 eng d a1381-199100a2D-QSAR modeling and two-fold classification of 1,2,4-triazole derivatives for antitubercular potency against the dormant stage of Mycobacterium tuberculosis0 a2DQSAR modeling and twofold classification of 124triazole deriva cAPR a1227-12420 v263 a

The dormant or latent form of Mycobacterium tuberculosis (MTB) is not killed by the conventional antitubercular drugs. The treatment of latent TB is essential to reduce the period of treatment as well as incidences of drug resistance. In this background, we have made an attempt to develop the quantitative structure-activity relationship models (QSAR: regression and classification based) against the dormant form of MTB and later used the developed classifier models (linear discriminant analysis (LDA) and random forest (RF)) for the two-fold classifications. The logic of applying this concept of two-fold classification for the MTB modeling is to increase the confidence of correct classification. The 2D-QSAR modeling suggested the contribution of burden eigen, edge adjacency, van der Waals (vdW) surface area, topological charge, and pharmacophoric indices in predicting the antitubercular activity against the dormant MTB. The prediction qualities of the training and test sets were found to be moderate and good, according to the mean absolute error (MAE)-based criteria's. The LDA and RF models unveiled the importance of burden eigen, edge adjacency, Geary autocorrelation, and drug-like indices as discriminating features to differentiate the antitubercular compounds into higher and lower active groups. The LDA model showed the classification accuracies of 85.14% and 87.10% for the training and test sets, while the RF model exhibited the accuracies of 100.00% and 80.65% for both the sets. The descriptors selected in the final models are only two-dimensional (2D), which are easy to compute and does not require computationally expensive steps of structure conversion, optimization, and energy minimization mandatorily needed before the computation of 3D descriptors. These models could be used for identifying and selection of higher active compounds against the dormant form of the MTB.

10aClassification models10aDormant TB10aLinear discriminant analysis (LDA)10aMycobacterium tuberculosis (MTB)10aNonlinear modeling10aQSAR10aRandom forest (RF)1 aAher, Rahul, Balasaheb1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/2d-qsar-modeling-and-two-fold-classification-124-triazole-derivatives-antitubercular-potency02401nas a2200301 4500008004100000022001400041245011100055210006900166260000800235300001200243490000700255520143200262653001301694653002201707653002501729653000901754653001401763100002301777700002701800700002101827700002201848700002201870700002301892700001901915700002301934700001701957856012501974 2021 eng d a1573-409900aIn silico studies, synthesis and antitubercular activity of some novel quinoline - azitidinone derivatives0 aIn silico studies synthesis and antitubercular activity of some  cJAN a134-1430 v173 a

Background: Diarylquinolines like Bedaquiline have shown promising antitubercular activity by their action of Mycobacterial ATPase. Objective: The structural features necessary for a good antitubercular activity for a series of quinoline derivatives were explored through computational chemistry tools like QSAR and combinatorial library generation. In the current study, 3-Chloro-4-(2-mercaptoquinoline-3-yl)-1-substitutedphenylazitidin-2-one derivatives have been designed and synthesized based on molecular modeling studies as anti-tubercular agents. Methods: 2D and 3D QSAR analyses were used to designed compounds having a quinoline scaffold. The synthesized compounds were evaluated against active and dormant strains of Mycobacterium tuberculosis (MTB) H37 Ra and Mycobacterium bovis BCG. The compounds were also tested for cytotoxicity against MCF-7, A549 and Panc-1 cell lines using MTT assay. The binding affinity of designed compounds was gauged by molecular docking studies. Results: Statistically significant QSAR models generated by the SA-MLR method for 2D QSAR exhibited r(2) = 0.852, q(2) = 0.811, whereas 3D QSAR with SA-kNN showed q(2) = 0.77. The synthesized compounds exhibited MIC in the range of 1.38-14.59(mu g/ml). These compounds showed some crucial interaction with MTB ATPase. Conclusion: The present study has shown some promising results which can be further explored for lead generation.

10acombilib10aMolecular docking10amycobacterial ATPase10aQSAR10aQuinoline1 aChitre, Trupti, S.1 aAsgaonkar, Kalyani, D.1 aVikhe, Amrut, B.1 aPatil, Shital, M.1 aGarud, Dinesh, R.1 aKhedkar, Vijay, M.1 aSarkar, Dhiman1 aNawale, Laxman, U.1 aYeware, Amar uhttps://library.ncl.res.in/content/silico-studies-synthesis-and-antitubercular-activity-some-novel-quinoline-azitidinone01522nas a2200193 4500008004100000245010600041210006900147260000800216300001400224490000700238520084100245100002001086700002101106700001501127700001901142700001901161700002101180856012701201 2021 eng d00aIn vitro antitubercular screening and in silico study of germacradienolide from blainvillea latifolia0 aIn vitro antitubercular screening and in silico study of germacr cJAN a3129-31330 v333 aBioassay-guided isolation from acetone extract of Blainvillea latifolia yielded one compound. The acetone extract, fractions and the compound 1 were investigated for antitubercular activity against Mycobacterium tuberculosis H37Ra. Compound 1 showed the activity with IC50 and MIC values at 8.9 and >100 μg/mL. However, the acetone extract of Blainvillea latifolia was inactive against two Gram negative (E. coli, P. flurescence) and two Gram-positive (S. aureus, B. subtilis) bacterial strains. Hence, it was concluded that the extract and the compound 1 are specifically active against MTB and not against bacterial strains. Molecular docking study was performed against crucial mycobacterial target MtInhA to gain an insight into the binding mode and the thermodynamic interactions governing the binding affinity of this molecule. 1 aHonmore, Varsha1 aKalyankar, Vidya1 aNatu, Arun1 aKhedkar, Vijay1 aSarkar, Dhiman1 aRojatkar, Supada uhttps://library.ncl.res.in/content/vitro-antitubercular-screening-and-silico-study-germacradienolide-blainvillea-latifolia01959nas a2200181 4500008004100000022001400041245012100055210006900176260000900245300001000254490000700264520130300271100001901574700002001593700001701613700001901630856012801649 2021 eng d a2045-232200aNovel gene similar to nitrite reductase (NO forming) plays potentially important role in the latency of tuberculosis0 aNovel gene similar to nitrite reductase NO forming plays potenti cOCT  a198130 v113 aThe development of the latent phenotype of Mycobacterium tuberculosis (Mtb) in the human lungs is the major hurdle to eradicate Tuberculosis. We recently reported that exposure to nitrite (10 mM) for six days under in vitro aerobic conditions completely transforms the bacilli into a viable but non-cultivable phenotype. Herein, we show that nitrite (beyond 5 mM) treated Mtb produces nitric oxide (NO) within the cell in a dose-dependent manner. Our search for the conserved sequence of NO synthesizing enzyme in the bacterial system identified MRA2164 and MRA0854 genes, of which the former was found to be significantly up regulated after nitrite exposure. In addition, the purified recombinant MRA2164 protein shows significant nitrite dependent NO synthesizing activity. The knockdown of the MRA2164 gene at mRNA level expression resulted in a significantly reduced NO level compared to the wild type bacilli with a simultaneous return of its replicative capability. Therefore, this study first time reports that nitrite induces dormancy in Mtb cells through induced expression of the MRA2164 gene and productions of NO as a mechanism for maintaining non-replicative stage in Mtb. This observation could help to control the Tuberculosis disease, especially the latent phenotype of the bacilli.1 aAgrawal, Sonia1 aGample, Suwarna1 aYeware, Amar1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/novel-gene-similar-nitrite-reductase-no-forming-plays-potentially-important-role-latency02146nas a2200157 4500008004100000020002200041245009200063210006900155260003000224300001400254520161800268100002701886700001901913700001501932856004101947 2021 eng d a978-1-0716-1366-500aOnline tools and antiviral databases for the development of drugs against coronaviruses0 aOnline tools and antiviral databases for the development of drug aNew York, NYbSpringer US a717–7343 aThe current crisis of coronavirus pandemic has created an urgent need for readily available scientific information to the researchers, students, professionals, and journalists. The scientific information for the research is costly, and most of the universities and research institutes cannot afford to subscribe to all the coronavirus-related journals/articles during this crisis time. In order to expedite the process of vaccine development and discovery of anti-COVID drugs, most of the pharmaceutical companies, research institutes and publishers are playing a key role and working on war footing to get either a vaccine or an anti-COVID drug as early as possible. The collective efforts are required from everyone in this testing time of the corona crisis. To provide our contribution to the scientific community, we have made here an attempt to give an overview of some of the tools and resources freely available that probably provide some insights in data mining and screening of novel lead molecules toward coronavirus. We have collected and compiled the information of open access online tools and antiviral databases essential for the discovery and development of corona vaccine and anti-COVID drugs. The open access tools include Open Educational Resources (OERs), Google cloud, online prediction server, web-based viewer, etc., while the antiviral databases include libraries of synthetic and untested compounds, antiviral drug databases, antiviral peptides, etc. The information presented in this chapter will help the researchers to use them directly in their projects of coronavirus drug discovery.1 aAher, Rahul, Balasaheb1 aSarkar, Dhiman1 aRoy, Kunal uhttps://doi.org/10.1007/7653_2020_4802695nas a2200265 4500008004100000022001400041245015600055210006900211260000800280300001200288490000700300520175900307653001502066653001502081653003102096653002202127653002702149653002702176653001802203653001702221653002202238100002702260700001902287856012302306 2021 eng d a0739-110200aPharmacophore modeling of pretomanid (PA-824) derivatives for antitubercular potency against replicating and non-replicating Mycobacterium tuberculosis0 aPharmacophore modeling of pretomanid PA824 derivatives for antit cFEB a889-9000 v393 a

Pretomanid (PA-824) is the recently (2019) approved drug for the treatment of extensively drug-resistant (XDR) TB and the multidrug-resistant (MDR) TB by US FDA. The experimental data of antitubercular activity of 543 pretomanid derivatives (total 6 datasets) against replicating (active) and non-replicating (dormant) forms of Mycobacterium tuberculosis (strain H37Rv) are available in the literature. Such vast experimental data of pretomanid derivatives against both of these endpoints, and recent approval of pretomanid molecule as a drug encouraged us to utilize this existing experimental information for the development of the 3D-pharmacophore models. The developed model (Hypo-1, MABA) showed the three physicochemical features namely, the oxygen atom of nitro group (HBA_1), fused pyran ring of imidazopyran heterocycle (HYAl_2) and the 4-fluorophenyl moiety (HYAr_3) are crucial for the antitubercular activity against replicating M. tb. Subsequently, the pharmacophore model (Hypo-1, LORA) developed against the non-replicating form of M. tb also showed the contribution of three physicochemical features namely, the 4-tri-fluoromethyl group (HYAl_2) and both the phenyl groups (HYAr_3, HYAr_4) of biaryl moiety in increasing the antitubercular activity. Both the pharmacophoric classifier models showed the classification accuracies of 82.98 and 74.42% for the training set compounds, and 63.91 and 61.60% for the test set compounds respectively, for labelling the compounds into higher and lower active classes. Both the models were also found to be retaining the higher active compounds in top 1.00% of the total number of compounds (decoys and actives), after performing the decoy set screening. Communicated by Ramaswamy H. Sarma

10aLORA assay10aMABA assay10aMycobacterium tuberculosis10anon-replicating M10apharmacophore modeling10apretomanid derivatives10areplicating M10atuberculosis10avirtual screening1 aAher, Rahul, Balasaheb1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/pharmacophore-modeling-pretomanid-pa-824-derivatives-antitubercular-potency-against00759nas a2200205 4500008004100000022001400041245012700055210006900182260000900251300001100260490000700271100002200278700002500300700002500325700001800350700002400368700001900392700002500411856011700436 2021 eng d a0960-894X00aSynthesis and cell imaging applications of fluorescent mono/di/tri-heterocyclyl-2,6-dicyanoanilines (vol 27, pg 979, 2017)0 aSynthesis and cell imaging applications of fluorescent monoditri cJAN  a1277370 v321 aPisal, Mahesh, M.1 aAnnadate, Ritesh, A.1 aAthalye, Meghana, C.1 aKumar, Deepak1 aChavan, Subhash, P.1 aSarkar, Dhiman1 aBorate, Hanumant, B. uhttps://library.ncl.res.in/content/synthesis-and-cell-imaging-applications-fluorescent-monoditri-heterocyclyl-2602099nas a2200253 4500008004100000022001400041245010600055210006900161260000800230300001100238490000800249520125600257653001701513653003101530653001301561653002201574100002301596700002001619700001901639700001901658700001901677700002301696856012601719 2021 eng d a0045-206800aSynthesis of new 2-(thiazol-4-yl)thiazolidin-4-one derivatives as potential anti-mycobacterial agents0 aSynthesis of new 2thiazol4ylthiazolidin4one derivatives as poten cOCT a1051920 v1153 aTo search for potent antimycobacterial lead compounds, a new series of 3-substituted phenyl-2-(2-(substituted phenyl)thiazol-4-yl) thiazolidin-4-one (5a-t) derivatives have been synthesized by the condensation of 2 substituted phenyl thiazole-4-carbaldehyde with aromatic amine followed by cyclocondensation with thioglycolic acid. The structure of the newly synthesized 2-(thiazol-4-yl)thiazolidin-4-one derivatives were characterized by the spectroscopic analysis. The synthesized compounds were screened for antimycobacterial activity against Mycobacterium tuberculosis H37Ra (MTB) (ATCC 25177) and Mycobacterium bovis BCG (BCG, ATCC 35743). Most of the 2-(thiazol-4-yl)thiazolidin-4-one derivatives showed good to excellent antimycobacterial activity against both the Mtb strains. Nine derivatives 5c, 5g, 5j, 5m, 5n, 5o, 5p, 5s, and 5t showed excellent activity against M. bovis BCG with MIC 4.43 to 24.04 mu M were further evaluated for the cytotoxicity activity against HeLa A549, and HCT-116 cell lines and showed no significant cytotoxic activity at the maximum concentration evaluated. The potential antimycobacterial activities enforced that the thiazolyl-thiazolidin-4-one derivatives could lead to compounds that could treat tuberculosis.10aCytotoxicity10aMycobacterium tuberculosis10aThiazole10aThiazolidin-4-one1 aAbhale, Yogita, K.1 aShinde, Abhijit1 aShelke, Monika1 aNawale, Laxman1 aSarkar, Dhiman1 aMhaske, Pravin, C. uhttps://library.ncl.res.in/content/synthesis-new-2-thiazol-4-ylthiazolidin-4-one-derivatives-potential-anti-mycobacterial02067nas a2200277 4500008004100000022001400041245012300055210006900178260000800247300001400255490000700269520108700276653003101363653003401394653001701428653001701445653002801462100003001490700002401520700002401544700002001568700002401588700001901612700002601631856013201657 2022 eng d a1040-663800aAmide-linked monocarbonyl curcumin analogues: efficient synthesis, antitubercular activity and molecular docking study0 aAmidelinked monocarbonyl curcumin analogues efficient synthesis  cMAY a2655-26710 v453 a

An approach toward the synthesis of novel conjugates of 3,5-bis (arylidene)-4-piperidones (DAP) pharmacophore with amide-linkage has been developed via one-pot multicomponent reaction of aryl aldehydes, piperidinone and 2-chloro-N-phenylacetamide using [Et3NH][HSO4] as a catalyst/medium. Both substitutions on arylidene rings and piperidinone nitrogen (substituted 2-chloro-N-phenylacetamide) were varied. The synthesized conjugates were evaluated for their in vitro antitubercular activity against M. tuberculosis H37Ra (MTB) and M. bovis BCG strains. Among the series, compounds 4f, 4g, 4i and 4j showed remarkable broad spectrum antitubercular activity with low IC50 values. Furthermore, computer docking simulations, for the most active conjugates were performed with the active site of mycobacterial enoyl-acyl carrier protein reductase (InhA) support the antitubercular activity. Lower cytotoxicity, high potency and promising activity against MTB and M. Bovis BCG suggest that amide linked DAP could serve as good leads for further modifications and development.

10aantimycobacterial activity10aBis (arylidene)-4-piperidones10aCytotoxicity10aIonic liquid10aMolecular docking Study1 aSubhedar, Dnyaneshwar, D.1 aShaikh, Mubarak, H.1 aNagargoje, Amol, A.1 aAkolkar, Satish1 aBhansali, Sujit, G.1 aSarkar, Dhiman1 aShingate, Bapurao, B. uhttps://library.ncl.res.in/content/amide-linked-monocarbonyl-curcumin-analogues-efficient-synthesis-antitubercular-activity-and02359nas a2200241 4500008004100000022001400041245012700055210006900182260000800251300001200259490000700271520148100278653002801759653004101787653002201828100002401850700001901874700002901893700002101922700002301943700001901966856013201985 2022 eng d a0272-439100aConventional and microwave-assisted organic synthesis of novel antimycobacterial agents bearing furan and pyridine hybrids0 aConventional and microwaveassisted organic synthesis of novel an cAPR a416-4310 v833 a

Drug resistance in tuberculosis poses a serious threat to humanity because currently available antitubercular drugs are ineffective against Mycobacterium tuberculosis (M. tuberculosis). As a result, the approval of Bedaquiline and Delamanid for the treatment of drug-resistant tuberculosis was accelerated. Still, there is an urgent need to search for new antitubercular drugs with novel mechanisms of action (MoA). Due to this, we have designed a synthetic strategy by utilizing microwave-assisted organic synthesis. We have compared our method with the conventional procedure, and the data show that our procedure is more effective in the preparation of title compounds. A unique series of 1-(2-(furan-2-yl)-5-(pyridin-4-yl)-1,3,4-oxadiazol-3(2H)-yl)-3-(aryl)-pr op-2-en-1-ones (5a-o) was synthesized utilizing conventional and microwave-assisted techniques. Synthetic compounds were investigated for antitubercular activity against Mycobacterium TB H37Ra and Mycobacterium bovis (M. bovis). Compound 5b was reported to be the most effective against M. tuberculosis H37Ra (97.69 percent inhibition at 30 mu g/ml) and M. bovis (97.09 percent inhibition at 30 mu g/ml). An in silico binding affinity study of mycobacterial enoyl-acyl carrier protein reductase (InhA) reveals the binding mechanism and thermodynamic interactions that determine these molecule's binding affinity. Compound 5b had a high glide score of -8.991 and low glide energy of -49.893 kcal/mol.

10aAntitubercular activity10amicrowave-assisted organic synthesis10aMolecular docking1 aDesai, Nisheeth, C.1 aBhatt, Kandarp1 aJadeja, Dharmpalsinh, J.1 aMehta, Harsh, K.1 aKhedkar, Vijay, M.1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/conventional-and-microwave-assisted-organic-synthesis-novel-antimycobacterial-agents-bearing01905nas a2200265 4500008004100000022001400041245014800055210006900203260000800272300001400280490000700294520096200301653002801263653001301291653001701304653001701321653002901338100003001367700002401397700002401421700001901445700002301464700002601487856012601513 2022 eng d a1040-663800a[DBUH][OAc]-catalyzed domino synthesis of novel benzimidazole incorporated 3,5-Bis (Arylidene)-4-piperidones as potential antitubercular agents0 aDBUHOAccatalyzed domino synthesis of novel benzimidazole incorpo cNOV a7010-70240 v423 a

A series of new benzimidazole incorporated 3,5-bis (arylidene)-4-piperidones were synthesized by using aryl aldehydes, piperidinone, 2-(chloromethyl)-benzimidazole and DBU acetate [DBUH][OAc] act as a catalyst under solvent free condition in excellent yields. The synthesized compounds were screened for their in vitro antimycobacterial activity against M. tuberculosis H37Ra (MTB) and M. bovis BCG strains. The compounds 4a, 4b, 4e, 4i, 4k and 4l are highly potent against both the strains. Most of the active compounds are non-cytotoxic against MCF-7, A549, HCT 116 and THP-1 cell lines. Furthermore, a molecular docking study of these compounds was carried out to investigate their binding pattern with the target, active site of mycobacterial enoyl-acyl carrier protein reductase (Inh A). Therefore, these compounds can be subjected for further optimization and drug development which could give promising chemical leads for treatment of TB.

10aAntitubercular activity10acurcumin10aCytotoxicity10aIonic liquid10amulticomponent reactions1 aSubhedar, Dnyaneshwar, D.1 aShaikh, Mubarak, H.1 aNagargoje, Amol, A.1 aSarkar, Dhiman1 aKhedkar, Vijay, M.1 aShingate, Bapurao, B. uhttps://library.ncl.res.in/content/dbuhoac-catalyzed-domino-synthesis-novel-benzimidazole-incorporated-35-bis-arylidene-402277nas a2200337 4500008004100000022001400041245011600055210006900171260000800240300001400248490000700262520120700269653000601476653000601482653002101488653001101509653003001520653002801550653003101578100001801609700001701627700002501644700002401669700001701693700002301710700002401733700002201757700002201779700001901801856011901820 2022 eng d a1381-199100aDetection of a target protein (GroEl2) in Mycobacterium tuberculosis using a derivative of 1,2,4-triazolethiols0 aDetection of a target protein GroEl2 in Mycobacterium tuberculos cOCT a2535-25480 v263 a

Herein, we identified a potent lead compound RRA2, within a series of 54 derivatives of 1,2,4-triazolethiols (exhibit good potency as an anti-mycobacterial agents) against intracellular Mycobacterium tuberculosis (Mtb). Compound RRA2 showed significant mycobactericidal activity against active stage Mycobacterium bovis BCG and Mtb with minimum inhibitory concentration (MIC) values of 2.3 and 2.0 mu g/mL, respectively. At MIC value, RRA2 compound yielded 0.82 log reduction of colony-forming unit (cfu) against non-replicating Mtb. Furthermore, RRA2 compound was selected for further target identification due to the presence of alkyne group, showing higher selectivity index (> 66.66 +/- 0.22, in non-replicating stage). Using ``click'' chemistry, we synthesized the biotin linker-RRA2 conjugate, purified with HPLC method and confirmed the conjugation of biotin linker-RRA2 complex by HR-MS analysis. Furthermore, we successfully pulled down and identified a specific target protein GroEl2, from Mtb whole-cell extract. Furthermore, computational molecular modeling indicated RRA2 could interact with GroEl2, which explains the structure-activity relationship observed in this study.

10a110a210a4-triazolethiols10aGroEl210aMycobactericidal activity10aMycobacterium bovis BCG10aMycobacterium tuberculosis1 aSarkar, Sampa1 aSwami, Sagar1 aSoni, Sarvesh, Kumar1 aHolien, Jessica, K.1 aKhan, Arshad1 aKorwar, Arvind, M.1 aLikhite, Anjali, P.1 aJoshi, Ramesh, A.1 aJoshi, Rohini, R.1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/detection-target-protein-groel2-mycobacterium-tuberculosis-using-derivative-12402593nas a2200229 4500008004100000022001400041245012400055210006900179260000900248300001600257490000700273520179100280100002002071700001602091700001902107700002302126700003002149700001602179700001902195700001902214856013002233 2022 eng d a1477-922600aDNA binding, antitubercular, antibacterial and anticancer studies of newly designed piano-stool ruthenium(ii) complexes0 aDNA binding antitubercular antibacterial and anticancer studies  cNOV  a16371-163820 v513 a

The chemotherapeutic potential of ruthenium(ii) complexes has recently attracted researchers' interest as antibacterial and anticancer agents. In this study, two novel half-sandwich imine-based Ru complexes ([Ru(p-cymene)Cl(L-1)][PF6] (Ru-1) and [Ru(p-cymene)Cl(L-2)][PF6] (Ru-2)) were reported for their deoxyribonucleic acid (DNA) binding and antitubercular, antibacterial, and anticancer activities. The molecular structure of Ru-2 was obtained by single-crystal X-ray crystallography. DNA interaction studies were conducted by UV-Vis absorbance and fluorescence spectral titration which gave rise to DNA binding constants (K-b) of 1.32 x 10(6) and 1.82 x 10(6) for Ru-1 and Ru-2, respectively and the Stern-Volmer binding constant (K-SV) values for Ru-1 and Ru-2 were 1.7763 x 10(4) M-1 and 7.6 x 10(3) M-1, respectively. The in vitro antitubercular activity was evaluated against Mycobacterium tuberculosis H37Ra. The antibacterial potential of both the Ru-complexes was examined against Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria. The half-maximal inhibitory concentration (IC50) values for the antitubercular activity of Ru-1 and Ru-2 were 4.87 +/- 1.32 mu M and 5.78 +/- 0.54 mu M, respectively. A cytotoxic study of these complexes was performed against the human breast cancer cell line (MCF-7) and the human embryonic kidney cell line (HEK293) (normal cells). The study revealed meaningful activity of the Ru-1 complex against (cancer) MCF-7 cells, while the viability of HEK293 (normal) cells in the presence of Ru-2 was higher as compared to a reference drug 5FU. We suggest that these kinds of Ru-complexes could have potential for application in metallopharmaceuticals.

1 aNavale, Govinda1 aSingh, Sain1 aAgrawal, Sonia1 aGhosh, Chandrachur1 aChoudhury, Angshuman, Roy1 aRoy, Partha1 aSarkar, Dhiman1 aGhosh, Kaushik uhttps://library.ncl.res.in/content/dna-binding-antitubercular-antibacterial-and-anticancer-studies-newly-designed-piano-stool02131nas a2200229 4500008004100000022001400041245011900055210006900174260000800243300001100251490000700262520136100269653003001630653000801660653002501668653001101693653001701704100001701721700001901738700001901757856012501776 2022 eng d a2590-098600aProbes and techniques used in active and the hypoxia-based dormant state of an antitubercular drug screening assay0 aProbes and techniques used in active and the hypoxiabased dorman cMAR a1001150 v133 aCurrent antitubercular drug therapy requires more than six months and is unable to kill latent or dormant forms of tuberculosis. Thus, it is a need of new drug therapy to fight against dormant tuberculosis. However, the major obstacle in the development of novel drugs for dormant tuberculosis is the lack of relevant screening systems and using reliable probes to measure growth inhibition. Until now, several probes used in active state assays are significantly determining the inhibitory effect against the active state of mycobacteria. The dormant condition assays are based on hypoxia-derived dormancy which include resazurin reduction assay, nitrite reductase assay, XTT reduction menadione assay and low oxygen recovery assay. Major probes used in those assays are colorimetric/fluorescent dyes, enzymatic activity, and reporter genes include luciferase and fluorescent proteins. Although these dormant assays are based on hypoxia-induced features and difficult to maintain for a longer duration. Also, they further complicated by growth detection and pursuit of high throughput screening criteria. Here we reviewed complications of probes and assay techniques used for anti-dormant drug screening programs of tuberculosis. This will provide the knowledge to design better alternative drug screening method for the anti-dormant form of tuberculosis.10aActive and dormant states10aand10aDrug screening assay10aProbes10atuberculosis1 aYeware, Amar1 aAkhtar, Shamim1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/probes-and-techniques-used-active-and-hypoxia-based-dormant-state-antitubercular-drug01555nas a2200253 4500008004100000022001400041245011200055210006900167520065400236653001500890653002700905653001700932653003100949653001400980653001300994100002701007700002301034700002401057700002401081700002301105700001901128700002201147856013201169 2022 eng d a1551-700400aSynthesis and antimycobacterial screening of a novel series of alpha-amino acids containing thiazole linker0 aSynthesis and antimycobacterial screening of a novel series of a3 a

A small focused library of uncommon (S)-2-amino-3-(4-(((4-methyl-2-arylthiazol-5-yl)methyl)amino)phenyl) propanoic acid (5a-e) and (S)-2-amino-3-(4-(((2-arylthiazol-4-yl)methyl)amino)phenyl)propanoic acid (9a-d) derivatives have been efficiently synthesized by employing molecular simplification. The title compounds were screened for inhibitory activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis (BCG) strains. The cytotoxicity study was conducted against primary Human Umbilical Vein Endothelial Cells (HUVECs), on two different human tumor cells HeLa, and HCT 116 and was observed non-toxic to host cells.

10aAmino acid10aantibacterial activity10aCytotoxicity10aMycobacterium tuberculosis10asynthesis10aThiazole1 aNalawade, Jitendra, L.1 aMhaske, Pravin, C.1 aShinde, Abhijit, D.1 aChavan, Abhijit, P.1 aAbhale, Yogita, K.1 aSarkar, Dhiman1 aBobade, Vivek, D. uhttps://library.ncl.res.in/content/synthesis-and-antimycobacterial-screening-novel-series-alpha-amino-acids-containing-thiazole02255nas a2200289 4500008004100000022001400041245013300055210006900188260000800257300001400265490000700279520128400286653001701570653002701587653003101614653001301645653001301658100002601671700002301697700002001720700002001740700002201760700002401782700001901806700002301825856011701848 2022 eng d a1040-663800aSynthesis of new thiazole and pyrazole clubbed 1,2,3-triazol derivatives as potential antimycobacterial and antibacterial agents0 aSynthesis of new thiazole and pyrazole clubbed 123triazol deriva cJUL a3216-32370 v423 a

New series of 4-methyl-2-(4-substituted phenyl)-5-(4-((4-(4-substituted phenyl)-1H-1,2,3-triazol-1-yl)methyl)-1-phenyl-1H-pyrazol-3-yl)thiazole, 6a-t and 4-(1,3-diphenyl-1H-pyrazol-4-yl)-1-((1,3-diphenyl-1H-pyrazol-4-yl)methyl )-1H-1,2,3-triazole, 11a-o derivatives have been synthesized by applying copper-catalyzed [3 + 2] cycloaddition reaction. The newly synthesized 1,3-thiazolyl-pyrazolyl-1,2,3-triazole (6a-t) and bis-pyrazolyl-1,2,3-triazole (11a-o) derivatives were screened for in vitro antimycobacterial activity against M. Tuberculosis H37Ra dormant and active and antibacterial activity against four pathogenic bacteria, E. coli (NCIM 2576), P. flurescence (NCIM 2059), S. aureus (NCIM 2602) and B. subtilis (NCIM 2162). Compounds 6a, 6f, 6j, 11e and 11m showed good activity against M tuberculosis H37Ra Active strain, also compounds 6g, 6h, 11f, 11n and 11o showed good activity against M tuberculosis H37Ra Dormant strain. Compounds 6b, 6i, 6l, 6o, 6r, 11k, 11l and 11m showed good activity against B. subtilis with IC50 1.99-2.96 mu g/mL. The antibacterial activity of thiazolyl-pyrazolyl-1,2,3-triazole and bis-pyrazolyl-1,2,3-triazole derivatives suggested that, these derivatives could lead to new compounds for treatment against bacterial infection.

10a123-Triazole10aantibacterial activity10aantimycobacterial activity10aPyrazole10aThiazole1 aJagadale, Shivaji, M.1 aAbhale, Yogita, K.1 aPawar, Hari, R.1 aShinde, Abhijit1 aBobade, Vivek, D.1 aChavan, Abhijit, P.1 aSarkar, Dhiman1 aMhaske, Pravin, C. uhttps://library.ncl.res.in/content/synthesis-new-thiazole-and-pyrazole-clubbed-123-triazol-derivatives-potential02341nas a2200301 4500008004100000022001400041245013600055210006900191260000800260300001400268490000700282520135600289653000601645653000601651653001501657653002001672653001801692653001601710653001801726100002401744700003001768700002401798700002401822700002301846700001901869700002601888856012501914 2022 eng d a1040-663800aTetrazoloquinoline-1,2,3-triazole derivatives as antimicrobial agents: synthesis, biological evaluation and molecular docking study0 aTetrazoloquinoline123triazole derivatives as antimicrobial agent cSEP a1920-19410 v423 a

In search of new active molecules, a small focused library of tetrazoloquinoline-based 1,2,3-triazoles has been efficiently preparedviaclick chemistry approach. Several derivatives were found to be exhibiting promising antimicrobial and antioxidant activity characterized by their lower minimum inhibitory concentration values. All the synthesized compounds exhibited excellent antibacterial activity against Gram negative bacteriaE. coliandF. devoransand antifungal activity againstC. albicansandA. niger. Further, these compounds were tested for their antitubercular activity against dormantMTB H37Raand dormantM. bovis BCGusing XRMA assay protocol and showed no significant activity. Also, the synthesized compounds were found to have potential antioxidant activity with IC(50)range = 12.48-50.20 mu g/mL. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against the active site of fungalC. albicansenzyme P450 cytochrome lanosterol 14 alpha-demethylase, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of thein vitroandin silicostudy suggest that the triazole-incorporated tetrazoloquinolines may possess the ideal structural requirements for further development of novel therapeutic agents.

10a110a210a3-Triazole10aADME prediction10aAntimicrobial10aAntioxidant10aDocking study1 aShaikh, Mubarak, H.1 aSubhedar, Dnyaneshwar, D.1 aAkolkar, Satish, V.1 aNagargoje, Amol, A.1 aKhedkar, Vijay, M.1 aSarkar, Dhiman1 aShingate, Bapurao, B. uhttps://library.ncl.res.in/content/tetrazoloquinoline-123-triazole-derivatives-antimicrobial-agents-synthesis-biological01924nas a2200277 4500008004100000022001400041245011200055210006900167260000800236300001400244490000700258520098200265653002701247653003101274653002201305653001501327653002201342653001901364100002401383700001901407700002301426700002401449700001901473700002501492856012901517 2022 eng d a1478-641900aTwo antibacterial spiro compounds from the roots of Artemisia pallens wall: evidence from molecular docking0 aTwo antibacterial spiro compounds from the roots of Artemisia pa cMAY a2465-24720 v363 a

Bioassay-guided isolation from acetone extract of the roots of Artemisia pallens Wall yielded two spiro compounds (1 and 2). The structures of these compounds were determined on the basis of spectroscopic techniques such as IR, MS, 1 D and 2 D- NMR. The acetone extract, fractions and the isolated two compounds were investigated for their antibacterial activity against two gram negative (E. coli, P. aeruginosa) and two gram positive (S. aureus, B. subtilis) bacterial strains. Compound (2) showed the best spectra of activity with IC50 and MIC values between 2.48-3.08 and 12.78 - 21.77 mu M and Compound (1) with 2.57-3.69 and 38.17 - 80.57 mu M, respectively, for the four bacterial strains, whereas inactive against Mycobacterium tuberculosis. Molecular docking study could further help in understanding the various interactions between these compounds and DNA gyrase active site in detail and thereby could provide valuable insight into the mechanism of action.

10aantibacterial activity10aantimycobacterial activity10aArtemisia pallens10aAsteraceae10aMolecular docking10aspiro compound1 aHonmore, Varsha, S.1 aNatu, Arun, D.1 aKhedkar, Vijay, M.1 aArkile, Manisha, A.1 aSarkar, Dhiman1 aRojatkar, Supada, R. uhttps://library.ncl.res.in/content/two-antibacterial-spiro-compounds-roots-artemisia-pallens-wall-evidence-molecular-docking03072nas a2200313 4500008004100000022001400041245014000055210006900195260000900264300001100273490000800284520201300292653001602305653002802321653002002349653001902369653002202388653002402410100001602434700002402450700001902474700002502493700002002518700001902538700002202557700002902579700001902608856013102627 2023 eng d a0141-813000aDesign and synthesis of piano-stool ruthenium(II) complexes and their studies on the inhibition of amyloid ? (1-42) peptide aggregation0 aDesign and synthesis of pianostool rutheniumII complexes and the cJUN  a1241970 v2393 a

Misfolding , protein aggregation have been linked to numerous human neurodegenerative disorders such as Alzheimer's, prion , Parkinson's diseases. Ruthenium (Ru) complexes have received considerable attention in studying protein aggregation due to their interesting photophysical and photo properties. In this study, we have synthesized the novel Ru complexes ([Ru(p-cymene)Cl(L-1)][PF6](Ru-1), and [Ru(p-cymene)Cl(L-2)][PF6](Ru-2)) and investigated their inhibitory activity against the bovine serum albumin (BSA) aggregation and the A beta 1-42 peptides amyloid formation. Several spectroscopic methods were used to characterize these complexes, and the molecular structure of the complex was determined by X-ray crystallography. Amyloid aggregation and inhi-bition activities were examined using the Thioflavin-T (ThT) assay, and the secondary structures of the protein were analyzed by circular dichroism (CD) spectroscopy and transmission electron microscopy (TEM). The cell viability assay was carried out on the neuroblastoma cell line, revealing that the complex Ru-2 showed better protective effects against A beta 1-42 peptide toxicity on neuro-2a cells than the complex Ru-1. Molecular docking studies elucidate the binding sites and interactions between the Ru-complexes and A beta 1-42 peptides. The exper-imental studies revealed that these complexes significantly inhibited the BSA aggregation and A beta 1-42 amyloid fibril formation at 1:3 and 1:1 molar concentrations, respectively. Antioxidant assays demonstrated that these complexes act as antioxidants, protecting from amyloid-induced oxidative stress. Molecular docking studies with the monomeric A beta 1-42 (PDB: 1IYT) show hydrophobic interaction, and both complexes bind preferably in the central region of the peptide and coordinate with two binding sites of the peptide. Hence, we suggest that the Ru-based complexes could be applied as a potential agent in metallopharmaceutical research against Alzheimer's disease.

10aAggregation10aAmyloid ?(1-42) peptide10aDFT computation10aFibrillization10aMolecular docking10aRuthenium complexes1 aSingh, Sain1 aNavale, Govinda, R.1 aAgrawal, Sonia1 aSingh, Haobam, Kisan1 aSingla, Labhini1 aSarkar, Dhiman1 aSarma, Manabendra1 aChoudhury, Anghuman, Roy1 aGhosh, Kaushik uhttps://library.ncl.res.in/content/design-and-synthesis-piano-stool-rutheniumii-complexes-and-their-studies-inhibition-amyloid02091nas a2200241 4500008004100000022001400041245016100055210006900216260000900285300001500294490000600309520119300315653002901508653002601537653001901563653003701582653001901619100001801638700001701656700001901673700002501692856013201717 2023 eng d a2365-654900aDesign, synthesis, and in vitro biological evaluation of ROS-generating phenanthridin-trione-epoxide conjugates as agents against mycobacterium tuberculosis0 aDesign synthesis and in vitro biological evaluation of ROSgenera cJUL  ae2023004160 v83 a

Tuberculosis (TB) is one of the devasting infectious diseases and continues to spread among people despite having several specific drugs. Total eradication of TB is one of the shared interests of both the World Health Organization (WHO) and India globally. A library of antitubercular 6-((1-(aryl/heteroaryl)-1H-1,2,3-triazol-4-yl)methyl)oxireno[2,3-b] phenanthridine-5,7,9(6H,7aH,8aH)-trione (6 a-e) has been prepared in five steps including click chemistry and tested against active and dormant strains of Mycobacterium tuberculosis H37Ra using XRMA protocol. The result showed the inhibitory potential of 6 d IC50 at 0.74 & mu;g/mL concentration against active strain and at 0.9 & mu;g/mL against the dormant strain of Mtb. ROS generating ability of the compounds has been confirmed by luminol, H2O2, and glutathione assays. The molecular docking with the thioredoxin protein of Mtb showed a docking score of -9.6 Kcal/mol. To understand the mechanism with the thioredoxin protein of Mtb, the adduct formation of compounds with cystine was confirmed with HPLC. The involvement of lead molecules with existing drugs can be helpful in the eradication of tuberculosis.

10aantimycobacterial agents10aComputational docking10aCystine adduct10aEpoxy-Phenanthridinone-triazoles10aROS generation1 aMamgain, Ritu1 aSwami, Sagar1 aSarkar, Dhiman1 aSrivastava, Pratibha uhttps://library.ncl.res.in/content/design-synthesis-and-vitro-biological-evaluation-ros-generating-phenanthridin-trione-epoxide02379nas a2200277 4500008004100000022001400041245010700055210007000162260000900232300001100241490000800252520144600260653002501706653003801731653002201769100001701791700002401808700001601832700002501848700001901873700001901892700001901911700002201930700001901952856013001971 2023 eng d a0141-813000aInhibition of amyloid β1-42 peptide aggregation by newly designed cyclometallated palladium complexes0 aInhibition of amyloid β142 peptide aggregation by newly designed cSEP  a1258470 v2483 a

Uncontrolled amyloid aggregation is a frequent cause of neurodegenerative disorders such as prions and Alzheimer's disease (AD). As a result, many drug development approaches focus on evaluating novel molecules that can alter self-recognition pathways. Herein, we designed and synthesized the cyclometallated pyrene (Pd-1 and Pd-3) and anthracene (Pd-2) based palladium complexes ([Pd((L-1)Cl] Pd-1, [Pd(L-2)Cl](Pd-2), and [Pd(L-3)Cl] (Pd-3)). This study explores the effect of these complexes on the aggregation, fibrillation, and amyloid formation of bovine serum albumin (BSA) and A beta(1-42) peptide. Several spectroscopic methods were used to characterize all the Pd-complexes, and the molecular structure of Pd -3 was determined by X-ray crystallography. The secondary structures were studied using circular dichroism (CD) and transmission electron microscopy (TEM), while am-yloid aggregation and inhibitory activities were investigated using the Thioflavin-T (ThT) fluorescence assay. Molecular docking of the Pd-complex (Pd-3) was done using fibril (PDB: 2BEG) and monomeric (PDB: 1IYT) peptides using Auto-dock Vina. As a result, the hydrogen bonding and hydrophobic interaction between the aromatic rings of the Pd-complexes and the amino acids of amyloid-beta peptides significantly reduced the pro-duction of ordered beta-sheets of amyloid fibrils and protein aggregation in the presence of Pd-2 and Pd-3 complexes.

10aA beta(1-42) peptide10aAggregation and molecular docking10aPalladium complex1 aSaini, Rahul1 aNavale, Govinda, R.1 aSingh, Sain1 aSingh, Haobam, Kisan1 aChauhan, Rahul1 aAgrawal, Sonia1 aSarkar, Dhiman1 aSarma, Manabendra1 aGhosh, Kaushik uhttps://library.ncl.res.in/content/inhibition-amyloid-%CE%B21-42-peptide-aggregation-newly-designed-cyclometallated-palladium02240nas a2200205 4500008004100000022001400041245015900055210006900214260000800283300001400291490000700305520147500312100001601787700001801803700001901821700001901840700003001859700002601889856011901915 2023 eng d a1477-052000aTotal synthesis, structure elucidation and expanded bioactivity of icosalide A: effect of lipophilicity and ester to amide substitution on its bioactivity0 aTotal synthesis structure elucidation and expanded bioactivity o cJUL a5725-57310 v213 a

The first total synthesis of icosalide A, an antibacterial depsipeptide that is unique in that it contains two lipophilic beta-hydroxy acids, has been achieved by following Fmoc solid-phase peptide synthesis in combination with solution-phase synthesis. The ambiguity in the absolute stereochemistry of icosalide A has been resolved by synthesizing the reported structures and other relevant diastereomers of icosalides and comparing their NMR data. NMR-based structure elucidation of icosalide A revealed a well-folded structure with cross-strand hydrogen bonds similar to the anti-parallel beta-sheet conformation in peptides and displayed a synergistic juxtaposition of the aliphatic sidechains. 12 analogues of icosalide A were synthesized by varying the constituent lipophilic beta-hydroxy acid residues, and their biological activities against Bacillus thuringiensis and Paenibacillus dendritiformis were explored. Most of these icosalide analogues showed an MIC of 12.5 & mu;g mL(-1) against both bacteria. Swarming inhibition by icosalides was least in B. thuringiensis (8.3%) compared to that in P. dendritiformis (33%). Furthermore, this is the first report of icosalides showing assured inhibitory action (MIC between 2 and 10 & mu;g mL(-1)) against the active stage of Mycobacterium tuberculosis and cancer cell lines such as HeLa and ThP1. This study could help optimize icosalides for anti-TB, antibacterial, and anti-cancer activities.

1 aDangi, Abha1 aPande, Bharat1 aAgrawal, Sonia1 aSarkar, Dhiman1 aVamkudoth, Koteswara, Rao1 aMarelli, Udaya, Kiran uhttps://library.ncl.res.in/content/total-synthesis-structure-elucidation-and-expanded-bioactivity-icosalide-effect02258nas a2200265 4500008004100000022001400041245016900055210006900224260000900293300001200302490000700314520130000321653002001621653002701641653002401668653002201692100002301714700002001737700002301757700002201780700002201802700001901824700002301843856012601866 2024 eng d a1040-663800aSynthesis and antimicrobial evaluation of novel 2'-aryl-4-aryl-2,4'-Bisthiazole and 2'-aryl-4-Pyridyl-2,4'-bisthiazole derivatives as potential antibacterial agents0 aSynthesis and antimicrobial evaluation of novel 2aryl4aryl24Bist cFEB  a773-7870 v443 a

In continuation of our research work to explore bisthiazole derivatives as potential antimicrobial agents, herein we reported the synthesis of a series of novel 2'-aryl-4-aryl-2,4'-bisthiazole (7a-t) and 2'-aryl-4-pyridyl-2,4'-bisthiazole (9a-l) by cyclocondensation of 2-aryl thiazole-4-carbothioamide 5a-d with 2-bromo-1-arylethanone (6a-e) and bromo-1-(pyridin-2/3/4-yl)ethanone (8a-c), respectively. These novel candidates were evaluated in vitro for their antibacterial potential against four pathogenic bacteria, Escherichia coli (NCIM 2576), Pseudomonas flurescence (NCIM 2059), Staphylococcus aureus (NCIM 2602), and Bacillus subtilis (NCIM 2162). The synthesized compounds were also screened for their in vitro antifungal activity against Candida albicans (NCIM 3100). Among them, compounds 7b, 9d, 9 g, 9i, and 9 l exhibited excellent antibacterial activity with MIC 2.1 to 12.3 mu g/mL against all tested strains. Most of the compounds reported moderate antifungal activity. The pyridine ring-substituted bisthiazole reported good to excellent antibacterial activity as compared to phenyl ring-substituted bisthiazole. The potential antibacterial activity suggested that bisthiazole derivatives could assist in the development of lead compounds to treat microbial infections.

10a24'-bisthiazole10aantibacterial activity10aAntifungal activity10acyclocondensation1 aNalawade, Jitendra1 aShinde, Abhijit1 aAbhale, Yogita, K.1 aNandurkar, Yogesh1 aBobade, Vivek, D.1 aSarkar, Dhiman1 aMhaske, Pravin, C. uhttps://library.ncl.res.in/content/synthesis-and-antimicrobial-evaluation-novel-2-aryl-4-aryl-24-bisthiazole-and-2-aryl-402519nas a2200301 4500008004100000022001400041245009900055210006900154260000800223300001400231490000700245520150600252653002701758653002601785653002501811653003001836653004201866653003001908100001901938700001701957700002201974700001701996700001902013700001902032700002002051700001702071856012902088 2025 eng d a1756-891900aCoumarin hybrids: dual-target candidates for future antimicrobial and antitubercular therapies0 aCoumarin hybrids dualtarget candidates for future antimicrobial  cMAY a1131-11420 v173 a

Aims: This study aimed to synthesize, characterize, and evaluate the antimicrobial and antitubercular activities of two novel series of coumarin-based derivatives (Series 5 and Series 9), focusing on their structure-activity relationship (SAR) and molecular docking interactions with key bacterial enzymes. Materials & methods: Series 5 (5a-5j) and Series 9 (9a-9t) compounds were synthesized and characterized using spectroscopic techniques. Their antimicrobial and antitubercular activities were evaluated against Mycobacterium tuberculosis, Staphylococcus aureus, Bacillus subtilis, and E. coli. IC50 values were determined, and molecular docking studies were conducted to assess binding interactions with M. tuberculosis enoyl-ACP reductase (InhA) and E. coli DNA gyrase B. Results: Series 5 compounds exhibited moderate activity, with 5f, 5 g, 5i, and 5j showing notable inhibition. Series 9 derivatives displayed superior dual-target inhibition, with 9t, 9c, 9a, 9b, and 9p achieving >90% inhibition against S. aureus and B. subtilis. The lowest IC50 against M. tuberculosis was observed for 9c (1.50 mu g/mL), followed by 9a (2.84 mu g/mL) and 9b (2.73 mu g/mL). Molecular docking confirmed strong binding interactions, correlating with observed biological activities. Conclusions: Series 9 compounds, particularly 9t, 9c, and 9a, demonstrate high potential as dual-target antimicrobial drug candidates. Further optimization may enhance their therapeutic efficacy. [GRAPHICS]

10aAntimicrobial activity10aantitubercular agents10aCoumarin derivatives10aMolecular docking studies10astructure-activity relationship (SAR)10athiophene-based compounds1 aBavishi, Abhay1 aVala, Hardev1 aThakrar, Shailesh1 aSwami, Sagar1 aSarkar, Dhiman1 aShukla, Rushit1 aKamdar, Jignesh1 aShah, Anamik uhttps://library.ncl.res.in/content/coumarin-hybrids-dual-target-candidates-future-antimicrobial-and-antitubercular-therapies02372nas a2200277 4500008004100000022001400041245013700055210006900192260000800261300001200269490000700281520140800288653000601696653002101702653002801723653002201751653002901773653001701802100003001819700002401849700002401873700001901897700002301916700002601939856012901965 2025 eng d a1385-272800a[DBUH][HSO4]-catalyzed solvent-free synthesis of 1,5-benzodiazepine derivatives: bioevaluation and in silico molecular docking study0 aDBUHHSO4catalyzed solventfree synthesis of 15benzodiazepine deri cJAN a226-2370 v293 a

Here, we report the solvent-free one-pot multicomponent synthesis of 4-substituted-1,5-benzodiazepine derivatives from O-phenylenediamine, aromatic aldehydes, and dimedone using [DBUH][HSO4] as a catalyst in excellent yields. This process was carried out in search of a reusable, easily accessible, affordable, and efficient catalyst. 1,5-Benzodiazepines demonstrate a new family of good inhibitors with potent anti-mycobacterial properties. The most promising compounds in the present series are 4c, 4i, and 4l which showed excellent activity and inhibited the growth of both MTB H37Ra and M. bovis BCG strains with lower MICs. The most active compounds were further studied for their cytotoxicity against cell lines MCF-7, A549, HCT116, and THP-1 by MTT assays and the compounds were found to be non-toxic. The fact that none of these compounds work against either Gram-positive or Gram-negative bacteria suggests that they are only effective against MTB. The in silico docking of the molecules against mycobacterial enoyl reductase, InhA enzyme could provide well-clustered solutions and have given valuable insights into the thermodynamic elements governing the binding affinities. The findings of this investigation unmistakably point to the discovery of extremely specific and selective MTB inhibitors, which can now be investigated further in search of possible anti-tubercular drugs.

10a110a5-benzodiazepine10aAntitubercular activity10aMolecular docking10amulticomponent reactions10a[DBUH][HSO4]1 aSubhedar, Dnyaneshwar, D.1 aShaikh, Mubarak, H.1 aNagargoje, Amol, A.1 aSarkar, Dhiman1 aKhedkar, Vijay, M.1 aShingate, Bapurao, B. uhttps://library.ncl.res.in/content/dbuhhso4-catalyzed-solvent-free-synthesis-15-benzodiazepine-derivatives-bioevaluation-and02287nas a2200289 4500008004100000022001400041245012500055210006900180260000800249300001200257490000700269520132000276653004001596653002701636653002801663653002601691653001001717653001401727653001301741100001901754700001701773700001701790700002201807700001701829700001901846856013201865 2025 eng d a0022-152X00aRegio selective synthesis of pyrazole derivatives of 5-chloro-2-methoxy phenyl hydrazide and their biological evaluation0 aRegio selective synthesis of pyrazole derivatives of 5chloro2met cAPR a325-3290 v623 a

Present study involves synthesis of derivatives of (5-chloro-2-methoxyphenyl) (5-alkyl-3-(substituted) (phenyl/alkyl)-1H-pyrazol-1-yl) methanones. Structural elucidation of the synthesized compounds was depicted by the data of 1H and 13C NMR, IR, and Mass spectral analysis. The newly synthesized compounds 1a-1d and 2a-2i were screened in vitro against Mycobacterium tuberculosis H37Ra using an established XRMA protocol. Among the screened compounds, 2d, 2f, and 2h showed good percent inhibition against the active stage of M. tuberculosis H37Ra 80.77, 55.70, and 79.54, respectively, at 30 mu g/mL of inhibitor concentration. Further in secondary screening, compound 2d exhibited significant antitubercular activity on the active stage of M. tuberculosis H37Ra with IC50 of 0.208 mu g/mL. The synthesized compounds were also screened for antibacterial activity and found no significant activity against Gram-positive Bacteria Bacillus subtitles and Staphylococcus aureus and Gram negative bacteria Pseudomonas aeruginosa and Escherichia coli at 30 mu g/mL, which confirms the specificity of inhibitory activity against M. tuberculosis and more selectively against the active stage. The present study will be helpful for the further development of these molecules into antitubercular lead candidates.

10a5-chloro-2-methoxy phenyl hydrazide10aantibacterial activity10aAntitubercular activity10aBiological evaluation10aH37Ra10ahydrazide10aPyrazole1 aBavishi, Abhay1 aVala, Hardev1 aSwami, Sagar1 aThakrar, Shailesh1 aShah, Anamik1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/regio-selective-synthesis-pyrazole-derivatives-5-chloro-2-methoxy-phenyl-hydrazide-and-their02453nas a2200289 4500008004100000022001400041245013400055210006900189260000800258300001500266490000700281520151600288653000601804653002201810653002301832653002401855653002101879653001301900100001901913700001701932700002101949700001701970700002201987700001902009700001702028856011802045 2025 eng d a2365-654900aSynthesis, biological screening, and molecular docking of hybrid pyrazole scaffolds for antitubercular and antimicrobial activity0 aSynthesis biological screening and molecular docking of hybrid p cJAN ae2024048300 v103 a

This study reports the synthesis, characterization, and docking analysis of 21 novel compounds, including asymmetric dihydropyridines (4a-4o) and chalcones (6a-6f), derived from coupling 1,3-(substituted)-diphenyl-1H-pyrazole-4-carbaldehyde with active methylene compounds and 3-acetyl-4-hydroxycoumarin, respectively. Structural confirmation was achieved through 1H and 13C NMR, IR, and mass spectrometry. Biological screening against mycobacterium tuberculosis H37Ra identified compounds 4b, 4d, 4f, 4g , 4i, 4k, 6e, and 6f as significant antitubercular agents. Antibacterial evaluation at 30 mu g/mL showed selective inhibition of gram-positive bacteria, with compound 6e active against Staphylococcus aureus and Bacillus subtilis, and 6f showing activity specifically against S. aureus. Docking studies indicated effective InhA binding (Delta G = -3.52 to -7.27 kcal/mol) and inhibition constants ranging from 2640 to 4.71 mu M. Key binding interactions with residues TYR156 and ILE192 were observed, enhancing affinity, particularly for compound 6e. The SAR analysis emphasized the enhanced antitubercular potency of 2-chloroacetyl and 2,4-dichlorobenzoyl substitutions in the dihydropyridine series, while in the chalcone series, specific substitutions, such as the 3-nitro substitution in 6e, enhance antitubercular and antimicrobial potency due to stronger hydrogen bonding and increased polar surface area, while the 4-fluoro substitution in 6f confers selective activity against S. aureus.

10a110a4-dihydropyridine10a4-hydroxy coumarin10aBiological activity10aIn silco studies10aPyrazole1 aBavishi, Abhay1 aVala, Hardev1 aRadadiya, Ashish1 aSwami, Sagar1 aThakrar, Shailesh1 aSarkar, Dhiman1 aShah, Anamik uhttps://library.ncl.res.in/content/synthesis-biological-screening-and-molecular-docking-hybrid-pyrazole-scaffolds