Design and evaluation of novel triazole derivatives as potential anti-gout inhibitors: A comprehensive molecular modeling study

This study presents a comprehensive investigation in the field of medicinal and computational chemistry, focusing on the design and evaluation of xanthine oxidase (XO) inhibitors based on triazole derivatives. The main objective is to explore new potential anti-hyperuricemic agents targeting XO inhibition, which remains a significant challenge in the treatment of gout and related metabolic disorders. The methodology employed includes a combination of computational approaches, such as 3D-QSAR (CoMFA and CoMSIA), molecular docking, molecular dynamics (MD) simulations, ADMET predictions, and DFT-based electronic structure analyses. These in silico techniques were used to investigate the structural and electronic properties of the studied compounds and to predict their biological activity and pharmacokinetic behavior. The results demonstrate a strong correlation between structural features of triazole derivatives and their predicted inhibitory activity against xanthine oxidase, highlighting key structure–activity relationships governing binding affinity and molecular recognition. In addition, theoretical calculations and simulations provided deeper insight into electronic properties, intermolecular interactions, and stability of ligand–enzyme complexes, supporting the identification of key pharmacophoric features responsible for activity. Overall, this work contributes to advancing knowledge in the field of computational drug design and xanthine oxidase inhibition, offering potential applications in pharmaceutical development for the treatment of gout and hyperuricemia. These findings may open new perspectives for future research aimed at the rational design of more potent and selective XO inhibitors.