In silico study of febuxostat analogs as inhibitors of xanthine oxidoreductase: A combined 3D-QSAR and molecular docking study

Abstract We explored molecular docking and a three-dimensional quantitative structure-activity relationship (3D-QSAR) model of 107 xanthine oxidoreductase (XOR) inhibitors containing a phenyl-substituted five-membered heterocycle. Molecular-docking results showed that Arg880, Phe914, and Phe1009 might be potential active residues targeted by the 107 XOR inhibitors evaluated in this study. Topomer comparative molecular field analysis (CoMFA) ( q 2  = 0.571; r 2  = 0.833) was used for 3D-QSAR. The results indicated that benzene substituted with moderately bulky substituents, a cyano group, and a five-membered heterocycle with a carboxyl group might enhance XOR inhibitory activity. Four new compounds were designed based on these results, and each exhibited potential XOR inhibitory activity in vitro .