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.

A 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 as PowerPoint slide