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

•24 Nitroimidazole derivatives have been synthesized.•Their biological activities were evaluated as potential antibacterial and selective FabH inhibitors for the first time.•Compounds 35 and 37 showed the most potent FabH inhibition.

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 Pseudomonas 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 β-ketoacyl-acyl carrier protein synthase III inhibitory assay and docking simulation indicated that compound 33 with IC50 of 9.0–36.4 μg/mL and compound 47 with IC50 of 6.3–34.3 μg/mL against bacterial strains were most potent inhibitors of E. coli FabH. And more, compounds 33 and 47 which possessed a broad-spectrum of antibacterial activities didn't exhibit any toxicity towards macrophage.

Graphical abstractA series of 2-ethanyl of 5-nitroimidazole derivatives have been synthesized and evaluated for their antibacterial activity as potential FabH inhibitors. Compounds 35 and 37 were the most active.Figure optionsDownload full-size imageDownload as PowerPoint slide