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- W2893083676 abstract "Antibiotic resistance among clinically significant bacterial pathogens is becoming a prevalent threat to public health, and new antibacterial agents with novel mechanisms of action hence are in an urgent need. Utilizing computational docking method and structure-based optimization strategy, we rationally designed and synthesized two series of isoxazol-3-yl- and isoxazol-5-yl-containing benzamide derivatives that targeted the bacterial cell division protein FtsZ. Evaluation of their activity against a panel of Gram-positive and -negative pathogens revealed that compounds B14 and B16 that possessed the isoxazol-5-yl group showed strong antibacterial activity against various testing strains, including methicillin-resistant Staphylococcus aureus and penicillin-resistant S. aureus. Further molecular biological studies and docking analyses proved that the compound functioned as an effective inhibitor to alter the dynamics of FtsZ self-polymerization via a stimulatory mechanism, which finally terminated the cell division and caused cell death. Taken together, these results could suggest a promising chemotype for development of new FtsZ-targeting bactericidal agent." @default.
- W2893083676 created "2018-10-05" @default.
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- W2893083676 date "2018-11-01" @default.
- W2893083676 modified "2023-09-25" @default.
- W2893083676 title "Design, synthesis and structure-based optimization of novel isoxazole-containing benzamide derivatives as FtsZ modulators" @default.
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- W2893083676 doi "https://doi.org/10.1016/j.ejmech.2018.09.053" @default.
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