Design and synthesis of potent inhibitors of beta-ketoacyl-acyl carrier protein synthase III (FabH) as potential antibacterial agents.

Twenty new Schiff bases were synthesized by reacting 5-fluoro-salicylaldehyde and primary amine as potent inhibitors of FabH. These compounds were assayed for antibacterial activity against Escherichia coli, Pseudomonas fluorescence, Bacillus subtilis and Staphylococcus aureus. Compounds with potent antibacterial activities were tested for their E. coli FabH inhibitory activity. (E)-4-fluoro-2-((4-hydroxyphenethylimino)methyl)phenol (10) showed the most potent antibacterial activity with MIC of 1.56-6.25 microg/mL against the tested bacterial strains and exhibited the most potent E. coli FabH inhibitory activity with IC(50) of 2.7 microM. Docking simulation was performed to position compound 10 into the E. coli FabH active site to determine the probable binding conformation. 2010 Elsevier Masson SAS. All rights reserved.