SYNTHESIS AND IN-SILICO ASSESSMENT OF CHALCONE DERIVATIVES AGAINST BACILLUS SUBTILIS

Abstract

Chalcones are privileged flavonoid scaffolds with a broad spectrum of antimicrobial activity. In this study, a series of brominated chalcone derivatives (103, 116, 198 and 200) were synthesized by Claisen–Schmidt condensation followed by regioselective bromination using tetrabutylammonium tribromide (TBATB). The chemical structures were confirmed by FTIR, 1H NMR, 13C NMR and mass spectrometry. In-silico molecular docking was done using Molegro Virtual Docker against DNA gyrase sub-unit B (GyrB PDB ID: 6F86) to elucidate the antimicrobial mechanism of the compounds against Bacillus subtilis. The binding affinities calculated for all the synthesized derivatives were better than the standard reference drug ciprofloxacin (MolDock score: -93.74). Among these, Chalcone 116 showed the most promising binding energy (MolDock score: -106.05; Rerank score: -83.44) with important interactions to critical active-site residues such as Asn46, Gly77, Asp73 and Glu50, similar to the native co-crystallized ligand. These results suggest that strategic bromination optimizes target engagement at the GyrB ATP binding site, making Chalcone 116 a strong lead for further empirical validation as an antibacterial agent.