Design and synthesis of 2-styryl of 5-Nitroimidazole derivatives and antimicrobial activities as FabH inhibitors

摘要

A series of 2-Styryl-5-Nitroimidazole derivatives (25-48) have been synthesized and their biological activities were also evaluated against two Gram-negative bacterial strains: Escherichia coli and Pseudo-monas aeruginosa and two Gram-positive bacterial strains: Bacillus subtilis and Bacillus thuringiensis as potential FabH inhibitors. All the compounds were structurally determined by ~1H NMR, MS, and elemental analysis. E coli beta-ketoacyl-acyl carrier protein synthase III inhibitory assay and docking simulation indicated that compound 33 with IC_(50) of 9.0-36.4 mug/mL and compound 47 with IC50 of 6.3 -34.3 mug/mL against bacterial strains were most potent inhibitors of ?coli FabH. And more, compounds 33 and 47 which possessed a broad-spectrum of antibacterial activities didn't exhibit any toxicity towards macrophage.