Synthesis, molecular modeling and biological evaluation of PSB as targeted antibiotics Original Research Article

We described here the design, synthesis, molecular modeling, and biological evaluation of a series of peptide and Schiff bases (PSB) small molecules, inhibitors of Escherichia coli β-Ketoacyl-acyl carrier protein synthase III (ecKAS III). The initial lead compound was reported by us previously, we continued to carry out structure–activity relationship studies and optimize the lead structure to potent inhibitors in this research. The results demonstrated that both N-(2-(3,5-dichloro-2-hydroxybenzylideneamino)propyl)-2-hydroxybenzamide (1f) and 2-hydroxy-N-(2-(2-hydroxy-5-iodobenzylideneamino)propyl)-4-methylbenzamide (3e) posses good ecKAS III inhibitory activity and well binding affinities by bonding Gly152/Gly209 of ecKAS III and fit into the mouth of the substrate tunnel, and can be as potential antibiotics agent, displaying minimal inhibitory concentration values in the range 0.20–3.13 μg/mL and 0.39–3.13 μg/mL against various bacteria.