Searching for potential xanthine oxidase inhibitors from Vietnamese herb plants via computational studies

Gout, a prevalent form of inflammatory arthritis, affects individuals of all ages and is increasing worldwide. It is closely associated with hyperuricemia, a condition caused by excessive uric acid production. Xanthine oxidase (XO) inhibitors play a key role in managing hyperuricemia, making the discovery of new and effective inhibitors a priority in drug development. In this study, computational methods were employed to screen natural compounds for their potential to inhibit XO. A total of 4947 compounds derived from 71 Vietnamese medicinal herbs were subjected to molecular docking simulations, leading to the identification of eight candidates with strong binding affinities and favorable drug-likeness according to Lipinski's rule. To further validate these findings, molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations were performed. Five newly discovered compounds, namely salvianolic acid A, puerarol, ochnaflavone, and forsythensides A and B, showed lower predicted binding energies than topiroxostat, suggesting their potential for further exploration as putative XO inhibitors. Notably, Van der Waals forces predominated over electrostatic interactions in the binding of these top candidates. The residues Glu802, Arg880, Thr1010, and Glu1261 served as key contributors to ligand binding, forming strong hydrogen bonds and side-chain contacts with the inhibitors. These findings offer valuable mechanistic insights into the interaction between natural compounds and XO, and highlight potential candidates for the development of novel XO inhibitors.