期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 107, 期 -, 页码 133-152出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2015.10.047
关键词
Surflex docking; Pyrrolyl chalcones; Pyrrolyl isoxazoles; Pyrrolyl pyrazolines; Anti-tubercular activity; Cytotoxicity activity; Enzyme inhibition studies
资金
- Council of Scientific and Industrial Research, New Delhi, India [02(0139)/13/EMR-II]
We report here the synthesis, antibacterial and antitubercular evaluation of 61 novel pyrrolyl derivatives bearing pyrazoline, isoxazole and phenyl thiourea moieties. Molecular docking was carried out on enoyl ACP reductase from Mycobacterium tuberculsosis using Surflex-Dock, which is one of the key enzymes involved in type II fatty acid biosynthetic pathway of Mycobacterium tuberculosis, an attractive target for designing novel antitubercular agents. Docking analysis of the crystal structure of ENR performed using Surflex-Dock in Sybyl-X 2.0 software indicates the occupation of substituted pyrrolyi derivatives into hydrophobic pocket of InhA enzyme. Compounds 9b and 9d exhibited the highest antitubercular activity almost close to isoniazid (0.4 mu g/mL) with a MIC value of 0.8 mu g/mL. All other compounds showed the good activity with a MIC value of 6.25-100 mu g/mL. The compounds were further tested for mammalian cell toxicity using human lung cancer cell-line (A549) and were nontoxic. Some compounds exhibited inhibition activities against InhA. (C) 2015 Elsevier Masson SAS. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据