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

被引：17

作者：

Li, Xiaolei ^{[1
]}

Zhou, Haiyan ^{[1
]}

Mo, Xianwei ^{[1
]}

Zhang, Lei ^{[1
]}

Li, Jing ^{[1
]}

机构：

[1] South China Univ Technol, Sch Biol & Biol Engn, Guangzhou 510006, Guangdong, Peoples R China

来源：

JOURNAL OF MOLECULAR STRUCTURE | 2019年 / 1181卷

关键词：

Xanthine oxidoreductase inhibitors; Molecular docking; 3D-QSAR; Topomer CoMFA; PARTIAL LEAST-SQUARES; ACID-DERIVATIVES; TOPOMER COMFA; QSAR; BIOEVALUATION; SELECTION; DESIGN;

D O I：

10.1016/j.molstruc.2019.01.017

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

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 fivemembered 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. (C) 2019 Elsevier B.V. All rights reserved.

引用

页码：428 / 435

页数：8

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