期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 157, 期 -, 页码 1115-1126出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2018.08.068
关键词
Chimera drug design; Nitrofurans; Imidazoles; Antitubercular; Mycobacterium tuberculosis; Multidrug resistant; Selective antimycobacterial activity; Druglikeness
资金
- Russian Science Foundation [14-50-00069]
Within the general nitrofuran carboxamide chemotype, chimera derivatives incorporating diversely substituted imidazoles attached via an alkylamino linker were synthesized. Antimycobacterial evaluation against drug-sensitive M. tuberculosis H37Rv strain identified five active druglike compounds which were further profiled against patient-derived M. tuberculosis strains in vitro. One of the compounds displayed promising potent activity (MIC 0.8 mu g/mL) against one of such strains otherwise resistant to such first and second-line TB therapies as streptomycin, isoniazid, rifampicin, ethambutol, kanamycin, ethionamide, capreomycin and amikacin. The compound was shown to possess low toxicity for mice (LD50 = 900.0 +/- 83.96 mg/kg) and to be similarly efficacious to etambutol, in the mouse model of drug sensitive tuberculosis, and to neurotoxic cycloserine in mice infected with MDR tuberculosis. (C) 2018 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