Design, synthesis, and computational and biological evaluation of a novel chalcone derivative with potent antibacterial activity

The rapid emergence of multidrug-resistant bacterial strains necessitates the development of novel antibacterial agents with alternative structural scaffolds and mechanisms of action. Chalcones, as privileged pharmacophores with tunable electronic properties and documented biological activities, represent promising candidates for antimicrobial drug development. In this study, (2E, 4E)-1,5-diphenylpenta-2,4-dien-1-one was synthesized using a conventional aldol condensation reaction between acetophenone and cinnamaldehyde and structurally characterized using IR and NMR spectroscopy. Density functional theory calculations were performed to investigate its electronic structure, frontier molecular orbitals (HOMO–LUMO), and reactive sites to justify its potential biological activity. The antimicrobial efficacy of (2E,4E)-1,5-diphenylpenta-2,4-dien-1-one was assessed against Escherichia coliATCC 8739 and Staphylococcus aureusATCC 29737. The compound exhibited significant antibacterial activity against both bacterial strains with minimum inhibitory concentration values of 62.5 and 125 µg/mL against E. coli and S. aureus, respectively. Molecular docking analyses revealed favorable hydrogen bonding and hydrophobic interactions with bacterial target proteins, supporting experimental observations. These findings suggest that this novel chalcone derivative could potentially be used as an alternative antibacterial agent after further structural optimization and mechanistic validation studies.