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.