Membrane active 7-thiazoxime quinolones as novel DNA binding agents to decrease the genes expression and exert potent anti-methicillin-resistant Staphylococcus aureus activity

A novel class of 7-thiazoxime quinolones was developed as potential antimicrobial agents for the sake of bypassing resistance of quinolones. Biological assays revealed that some constructed 7-thiazoxime quinolones possessed effective antibacterial efficiency. Methyl acetate oxime derivative 6l exhibited 32-fold more active than ciprofloxacin against MRSA, which also possessed rapidly bactericidal ability and low toxicity towards mammalian cells. The combination use of 7-thiazoxime quinolone 6l and ciprofloxacin was able to improve antibacterial potency and effectively alleviate bacterial resistance. The preliminarily mechanism exploration revealed that compound 6l could destroy the cell membrane and insert into MRSA DNA to bind with DNA gyrase, then decrease the expression of gyrB and femB genes. The above results strongly suggested that methyl acetate oxime derivative 6l held a promise for combating MRSA infection. (C) 2021 Elsevier Masson SAS. All rights reserved.

Automated summary

A novel class of 7-thiazoxime quinolones has been developed as potential antimicrobial agents to combat quinolone resistance. Biological assays have shown that these compounds, particularly methyl acetate oxime derivative 6l, exhibit potent antibacterial activity against MRSA, with the ability to improve potency and alleviate bacterial resistance when used in combination with ciprofloxacin. The mechanism of action involves destroying the cell membrane, binding with DNA gyrase in MRSA DNA, and downregulating key genes, suggesting promise for combating MRSA infection.