Microwave-assisted Synthesis and Molecular Docking Study of Heteroaromatic Chalcone Derivatives as Potential Antibacterial Agents

摘要

In this study,a series of chalcone derivatives(1a-c)were synthesized via Claisen-Schmidt condensation,followed by aza-Michael addition to form pyrazoline derivatives(2a-c and 3a-c).The reaction was performed via microwave radiation to give excellent yields(77-93%)in 1-3.5 min.Microwave-assisted reaction of Fischer esterification of pyrazolines(2a-c and 3a-c)afforded heteroaromatic pyrazoline esters(4a-c)in high yield(83-96% in <2 min)compared to conventional reflux(55-79% in 30 min).Compounds la-c and 3a-c demonstrated excellent antibacterial activity against Staphylococcus aureus via disc diffusion assay with inhibition zone with 13 and 19 mm compared to a standard drug,ampicillin(11 mm).Structure activity relationship of lb and 3b were visualized via molecular docking interaction against 4pql protein of S.aureus with binding free energy-7.0 and-8.0 kcal/mol,respectively.This study is significant in drug discovery process particularly for pharmaceutical industries.