In Silico Study of Xanthine Oxidase Inhibitory Activity of Secondary Metabolites from Purple-Orange Sweet Potato (Ipomoea batatas L.) Leaves

Hyperuricemia is a pathological condition characterized by elevated uric acid levels in the blood due to purine metabolism disorders and is commonly associated with gout. Xanthine oxidase is a key enzyme in the conversion of hypoxanthine to uric acid, making it a primary target for hyperuricemia therapy. This study aimed to evaluate the inhibitory potential of eight secondary metabolites derived from purple-orange sweet potato (Ipomoea batatas L.) leaves against xanthine oxidase using an in silico approach. Molecular docking against the xanthine oxidase enzyme (PDB ID: 3NVW) revealed that cholest-4-en-3-one exhibited the strongest binding affinity, with a binding free energy of −10.47 kcal/mol and an inhibition constant of 20.99 nM. The compound formed hydrogen bonds with the Lys771 residue and hydrophobic interactions with Phe914 and Phe1009. Molecular dynamics simulations over 100 ns confirmed the structural stability of the cholest-4-en-3-one–xanthine oxidase complex, as indicated by low RMSD and RMSF values. Drug-likeness evaluation based on Lipinski’s Rule of Five and ADMET predictions showed favorable pharmacokinetic properties and non-toxic characteristics. These findings suggest that cholest-4-en-3-one is a promising natural xanthine oxidase inhibitor candidate and may serve as a potential alternative therapeutic agent for hyperuricemia. Further in vitro and in vivo studies are warranted to confirm its efficacy and safety