Design, one-pot synthesis, molecular docking study, and antibacterial evaluation of novel 2H-chromene based imidazo[1,2-a]pyridine derivatives as potent peptide deformylase inhibitors

Abstract

An efficient, environmentally friendly, one-pot three-component synthesis of a series of 2H-chromene-based imidazo[1,2-a]pyridines had been designed and were synthesized. This protocol was developed by the reaction of substituted 2H-chromene aldehydes and 2-aminopyridine in a mixture of nitroalkane and DMF under microwave irradiation at 60W, 100°C in 15 min with the presence of FeCl3 as the catalyst. The products were obtained in excellent yields with high functional group tolerance. All these compounds had been investigated further in vitro for evaluation of antibacterial potency by agar-well diffusion method against human pathogenic Gram-positive and Gram-negative bacteria, with the determination of minimum inhibitory concentration (MIC) values. Indeed, compound 13i strongly inhibited peptide deformylase (MIC = 16 μg/ml) in the Gram-negative Escherichia coli, in silico. From structure-activity relationships based on the biological and molecular docking results and the potent antibacterial activities, it could be stated that the selected synthetic compounds could be used as potent drugable antibacterial agents.