Docking and in silico ADMET analysis of flavone glucoside compounds as antioxidant agents

Natural products continue to serve as a rich source of structurally diverse compounds with significant therapeutic potential. Among them, flavonoids an important class of polyphenolic secondary metabolites are widely distributed in plants and have attracted considerable interest due to their broad spectrum of biological activities. These include antioxidant, anti-inflammatory, and anticancer effects, as well as the inhibition of key metabolic enzymes such as xanthine oxidase (XO). XO is a critical enzyme in purine catabolism, catalyzing the oxidation of hypoxanthine to xanthine and subsequently to uric acid, a process that also generates reactive oxygen species (ROS) as by-products. Overactivity of XO, and the resulting accumulation of uric acid and ROS, has been associated with various pathological conditions, including gout and oxidative stress-related disorders. Consequently, XO inhibition represents a promising strategy for therapeutic intervention.
In this study, we investigated the xanthine oxidase inhibitory potential of two flavone glucoside compounds : chavicol-1-O-(6′-O-methylmalonyl)-β-D-glucopyranoside and chavicol-1-O-(6′-O-acetyl)-β-D-glucopyranoside which were previously isolated from the aerial parts of Agastache rugosa. Molecular docking analysis was performed to evaluate their binding affinity toward the XO active site. Both compounds exhibited strong interactions with key active site residues, achieving docking scores of approximately -7 kcal/mol, which are comparable to that of the well-known XO inhibitor, quercetin. The docked ligands formed critical hydrogen bonds with residues such as Lys771 and Ser876, along with hydrophobic contacts within the enzyme's active pocket.
In addition, ADMET profiling was conducted to assess the pharmacokinetic and physicochemical properties of the compounds