01495nas 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-agents02623nas 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<p>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 &gt;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.</p>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-cpyrimidine