02428nas 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-001848nas 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-and02341nas 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-docking