Structural elucidation, molecular docking, and in silico ADMET assessment of antibacterial flavones from Dodonaea viscosa leaf extracts

Leaf crude extracts from Dodonaea viscosa was investigated for antimicrobial activity, ADMET properties, and their structures elucidated in this research. The crude extract exhibited varying levels of antibacterial activity against Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, and Klebsiella pneumoniae ATCC 700603. The inhibition zone was observed at 500 mg/ml against E. coli (18.01 ± 0.82 mm), followed by S. aureus (17.23 ± 0.57 mm) and K. pneumoniae (15.79 ± 0.56 mm). K. pneumoniae showed sensitivity at concentrations as low as 31.25 mg/ml, while E. coli and S. aureus showed inhibitory responses only at higher concentrations. Structural elucidation yielded three flavones, namely 5,4′-dihydroxy-3,6,7-trimethoxyflavone, 5-hydroxy-3,6,7,4′-tetramethoxyflavone, and 5-hydroxy-6,7,4′-trimethoxyflavone. 5-hydroxy-6,7,4′ trimethoxyflavone which are reported here for the first time from D. viscosa, this expands the known flavonoid profile of this species. Structural analysis of the flavones disclosed significant physicochemical features, such as molecular weight, heavy atom count, rotatable bonds, and aromatic atoms, accountable for their bioactivity and conformational versatility. In-silico ADMET prediction also established drug-likeness and pharmacokinetic promise of the compounds. The three flavones were evaluated for their antibacterial potential against E. coli (4HWP) and S. aureus (7D8I) using molecular docking analysis. 5,4′-Dihydroxy-3,6,7-trimethoxy flavone, 5-hydroxy-3,6,7,4′-tetramethoxy flavone, and 5-hydroxy-6,7,4′-trimethoxy flavone, demonstrated strong binding affinities through hydrogen bonding, hydrophobic interactions, π–π stacking, and π-cation interactions. 5,4′-Dihydroxy-3,6,7-trimethoxy flavone exhibited the highest docking score against E. coli (−8.7 kcal/mol), comparable to tetracycline (−8.1 kcal/mol). In S. aureus, docking scores ranged from −7.0 to −7.6 kcal/mol, with interactions occurring at residues similar to tetracycline (−8.2 kcal/mol). These findings indicate that flavone derivatives from D. viscosa effectively stabilize bacterial receptor complexes and possess potential as lead compounds for novel antibacterial agents to combat infections and antibiotic resistance.