Characterization of beddomeilactone amide as bacterial DNA gyrase inhibitor: in vitro evaluation and computational insights.

The rapid rise of antimicrobial resistance (AMR), marked by declining efficacy of existing antibiotics against bacterial pathogens, has become a serious global health threat. Increasing resistance in the Staphylococcus aureus pathogen urgently demands the development of effective novel antibacterial agents. In this study, we investigated the previously reported antibacterial beddomeilactone amide (3g) as a potential DNA gyrase inhibitor of S. aureus. The potent hit (3g) exhibited > 90% reduction in DNA supercoiling at an effective concentration of 100 µM. Further, computational studies including molecular docking and dynamics simulation showed that the 3g molecule exhibited a favourable binding affinity of -12.33 kcal/mol, reflecting predicted stable interactions with DNA gyrase. Moreover, Density functional theory (DFT) findings further revealed key electronic properties, frontier molecular orbitals, and chemical reactivity of the compounds. These findings underscore potent hit (3g) as a promising candidate for the development of an antibacterial agent against S. aureus by targeting DNA gyrase.