Design, synthesis and structure-based optimization of novel isoxazole-containing benzamide derivatives as FtsZ modulators

Add time:07/27/2019    Source:sciencedirect.com

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.

We also recommend Trading Suppliers and Manufacturers of 3-Chloro-N-(3-chlorophenyl)benzaMide, 97% (cas 10286-92-7). Pls Click Website Link as below: cas 10286-92-7 suppliers

Prev:Rh(III)-catalyzed C-H activation of primary benzamides and tandem cyclization with cyclic 2-diazo-1,3-diketones for the synthesis of isocoumarins
Next:The effect of cyclodextrin complexation on the fluorescence properties of ethyl-4′-dimethylaminobenzoate)