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.