化学
诺氟沙星
DNA旋转酶
抗菌活性
拓扑异构酶
加替沙星
洛美沙星
抗菌剂
最小抑制浓度
铵
亲脂性
环丙沙星
生物化学
细菌
大肠杆菌
有机化学
体外
抗生素
遗传学
生物
基因
作者
Joanna Fedorowicz,Cristina D. Cruz,Małgorzata Morawska,Krzesimir Ciura,Shella Gilbert-Girard,Liliana Mazur,Heidi Mäkkylä,Polina Ilina,Kirsi Savijoki,Adyary Fallarero,Päivi Tammela,Jarosław Sączewski
标识
DOI:10.1016/j.ejmech.2023.115373
摘要
A series of quaternary ammonium fluoroquinolones was obtained by exhaustive methylation of the amine groups present at the 7-position of fluoroquinolones, including ciprofloxacin, enoxacin, gatifloxacin, lomefloxacin, and norfloxacin. The synthesized molecules were tested for their antibacterial and antibiofilm activities against Gram-positive and Gram-negative human pathogens, i.e. Staphylococcus aureus and Pseudomonas aeruginosa. The study showed that the synthesized compounds are potent antibacterial agents (MIC values at the lowest 6.25 μM) with low cytotoxicity in vitro as assessed on the BALB 3T3 mouse embryo cell line. Further experiments proved that the tested derivatives are able to bind to the DNA gyrase and topoisomerase IV active sites in a fluoroquinolone-characteristic manner. The most active quaternary ammonium fluoroquinolones, in contrast to ciprofloxacin, reduce the total biomass of P. aeruginosa ATCC 15442 biofilm in post-exposure experiments. The latter effect may be due to the dual mechanism of action of the quaternary fluoroquinolones, which also involves disruption of bacterial cell membranes. IAM-HPLC chromatographic experiments with immobilized artificial membranes (phospholipids) showed that the most active compounds were those with moderate lipophilicity and containing a cyclopropyl group at the N1 nitrogen atom in the fluoroquinolone core.
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