Synthesis, Characterization, and Computational Insights of Flavone Derivatives as Promising Antimicrobial Agents

A series of flavone derivatives ( 6a – 6k ), with varying ─O functionalities, was synthesized and characterized using spectroscopic techniques. In vitro antimicrobial assay against a range of bacterial and fungal strains, including Gram‐positive ( Staphylococcus aureus and Streptococcus pyogenes ) and Gram‐negative bacteria ( Escherichia coli and Pseudomonas aeruginosa ), as well as fungal species ( Candida albicans and Aspergillus niger ), has demonstrated superior antibacterial activity against Gram‐negative bacteria by most derivatives. Interestingly, compounds 6b , 6c , and 6j exhibited the highest potency, with MIC values of 20 µg/mL against E. coli , 50 µg/mL against S. aureus , and 80 µg/mL against E. coli and A. niger , which is better than their respective standard drugs. The structural details and mechanistic insights of flavone derivatives 6a – 6k were assessed by computational studies, including DFT, molecular docking, and ADMET analysis. HOMO–LUMO analysis indicated compound 6b exhibited enhanced chemical reactivity, correlating with its superior antibacterial activity against E. coli . Molecular docking revealed strong binding affinities, especially for 6b and 6j , suggesting their potential as therapeutic agents. These compounds adhered to Lipinski's rule and displayed favorable ADMET properties. Molecular dynamics simulations of 6b showed stable binding within the 4PRV protein ( E. coli ) active site. This study highlights the potential of flavone derivatives as promising antimicrobial agents, offering a new avenue for combating antibiotic resistance.