科研之友
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摘要
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 5b (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 5b 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 5b than that against norfloxacin. Molecular docking demonstrated that 5b could effectively bind with topoisomeraseIV-DNA complexes, and quantum chemical studies theoretically elucidated the good antimicrobial activity of compound 5b. Preliminary experimental reaction mechanism exploration suggested that derivative 5b 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 5b is a promising antibacterial agent with membrane disruption abilities.
- 出版日期2018-5-23
- 单位西南大学
