Inhibition of Xanthine Oxidase by Orientin, a C-Glycosylated Flavonoid: Kinetic Characterization and Molecular Simulation.
Xanthine oxidase catalyzes the oxidation of hypoxanthine to xanthine. It further oxidizes xanthine to uric acid, making it an important target for treating hyperuricemia. This study focused on orientin as a model flavonoid for xanthine oxidase inhibition. We examined whether the C-glycosyl group changes its inhibitory potency, binding pattern, and predicted ADMET profile. In vitro enzyme activity was determined to be 364.79 ± 8.21 μM for the half-inhibitory concentration (IC50) of orientin. Kinetic analysis suggested a mixed-type inhibition pattern. Intrinsic fluorescence quenching further supported the interaction between orientin and XO. Molecular docking and molecular dynamics simulations provided structural insight into the binding mode and stability of the orientin-XO complex. ADMET analysis indicates that orientin has promising pharmaceutical properties. These findings provide a basis for future research focusing on structural optimization, metabolic transformation, and in vivo evaluation.