Synthesis, Biological Evaluation and In Silico Docking Studies of Aryl‐Substituted Chroman‐4‐one Ester Derivatives as Potential Antimicrobial Agents

ABSTRACT In this study, a library of aryl‐substituted chroman‐4‐one ester derivatives 8(a–k) was synthesized through a sequential approach involving condensation–cyclization, Suzuki–Miyuara coupling, followed by nucleophilic acyl substitution reaction. The structures were finalized by 1 H and 13 C NMR, and mass spectral data. Pure titled compounds were assessed their antimicrobial activity against a panel of Gram‐positive and Gram‐negative bacteria in addition to fungal strains using standard in vitro methods. Of these, the Compound 8a exhibited the highest antibacterial activity, with minimum inhibitory concentration (MIC) values range of 0.98–0.12 µg/mL against across the tested bacterial strains, which matched the activity of ciprofloxacin. However, the antifungal activity of Compound 8a , MIC values for which were the lowest among all the compounds, with values of 0.98 µg/mL for Candida albicans and 3.90 µg/mL for Aspergillus niger and Aspergillus flavus , was equivalent to fluconazole. Attributable to the strong electron‐withdrawing –CF 3 group increases lipophilicity, enhancing π–π interactions and binding affinity with microbial targets. The combined biological and computational results highlight the potential of these novel chroman‐4‐one ester derivatives as promising candidates for antimicrobial drug development. Docking study revealed that the Compounds 8a–k bind effectively to the bacterial enzyme DNA gyrase B (PDB ID: 1KZN) with molecular interactions that are comparable to that of ciprofloxacin. These interactions provide valuable insights into their mechanism of enzyme inhibition.