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

Abstract

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 1a–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 1b 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.