喹诺酮类
诺氟沙星
铜绿假单胞菌
苯并咪唑
拓扑异构酶
DNA旋转酶
抗菌剂
化学
微生物学
大肠杆菌
生物
组合化学
细菌
生物化学
抗生素
环丙沙星
有机化学
基因
遗传学
作者
Yanan Wang,Rammohan R. Yadav Bheemanaboina,Wei‐Wei Gao,Jie Kang,Gui‐Xin Cai,Cheng–He Zhou
出处
期刊:ChemMedChem
[Wiley]
日期:2018-04-16
卷期号:13 (10): 1004-1017
被引量:45
标识
DOI:10.1002/cmdc.201700739
摘要
Abstract A series of benzimidazole–quinolone hybrids as new potential antimicrobial agents were designed and synthesized. Bioactive assays indicated that some of the prepared compounds exhibited potent antibacterial and antifungal activities. Notably, 2‐fluorobenzyl derivative 5 b (ethyl 7‐chloro‐6‐fluoro‐1‐[[1‐[(2‐fluorophenyl)methyl]benzimidazol‐2‐yl]methyl]‐4‐oxo‐quinoline‐3‐carboxylate) showed remarkable antimicrobial activity against resistant Pseudomonas aeruginosa and Candida tropicalis isolated from infected patients. Active molecule 5 b could not only rapidly kill the tested strains, but also exhibit low toxicity toward Hep‐2 cells. It was more difficult to trigger the development of bacterial resistance of P. aeruginosa against 5 b than that against norfloxacin. Molecular docking demonstrated that 5 b could effectively bind with topoisomerase IV–DNA complexes, and quantum chemical studies theoretically elucidated the good antimicrobial activity of compound 5 b . Preliminary experimental reaction mechanism exploration suggested that derivative 5 b could not intercalate into DNA isolated from drug‐resistant P. aeruginosa , but was able to cleave DNA effectively, which might further block DNA replication to exert powerful bioactivities. In addition, compound 5 b is a promising antibacterial agent with membrane disruption abilities.
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