Metal-Free Synthesis of 2-Aminothiazole Functionalized Imidazo[1,2-a]pyridines as Antibacterial Agents

The present work describes the synthesis, characterization, and in silico studies of some new 2-aminothiazole functionalized imidazo[1,2-a]pyridines (1a-h). The targeted compounds were synthesized by the Hantzsch's thiazole reaction involving the condensation reaction of alpha-bromomethyl ketones with 1-(3-nitroimidazo[1,2-a]pyridin-2-yl)thiourea (2). The key precursor 2 was synthesized by four steps method using 2-aminopyridine and chloroacetic acid as commercially available starting materials. The synthesized compounds 1a-1h displayed considerable activity against Gram-positive bacteria. In particular, compound 1b (R=2,4-dichloro) and 1e (R=4-carbethoxy) exhibited significant activity against Staphylococcus aureus and Bacillus subtilis in comparison to the standard antibacterial drug Ampicillin. The molecular docking and DFT studies of synthesized compounds were used to study the binding modes of these compounds. The compounds showed excellent binding energy scores (-8.3 to -9.3 kcal/mol) when interacting 1KZN protein (Escherichia coli) with compounds were examined which are in agreement with in vivo antibacterial activity.