02099nas 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-agents02321nas 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-derivatives02623nas 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-cpyrimidine02531nas 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-12301926nas 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-agents02855nas 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-antitubercular02080nas 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-2