Discovery of novel xanthone derivatives as xanthine oxidase inhibitors

被引：32

作者：

Hu, Lina ^{[1
]}

Hu, Honggang ^{[1
]}

Wu, Weifeng ^{[2
]}

Chai, Xiaoyun ^{[1
]}

Luo, Jianfei ^{[1
]}

Wu, Qiuye ^{[1
]}

机构：

[1] Second Mil Med Univ, Sch Pharm, Dept Organ Chem, Shanghai 200433, Peoples R China

[2] Shanghai Sixth Peoples Hosp, Branch Hosp, Fengxian Dist Cent Hosp, Shanghai 201400, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 13期

关键词：

Xanthone; Derivatives; Synthesis; Xanthine oxidase; Molecular modeling; OXIDOREDUCTASE; ACID; GOUT;

D O I：

10.1016/j.bmcl.2011.04.140

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Xanthine oxidase is the key enzyme that catalyzes the oxidation of hypoxanthine to xanthine and then to uric acid. In this study, a series of xanthone derivatives were synthesized as effective and a new class of xanthine oxidase inhibitor. Compounds 8a, 8c, 8i, 8g and 8r showed good inhibition against xanthine oxidase. The presence of a cyano group at the para position of benzyl moiety turned out to be the preferred substitution pattern. Molecular modeling studies were performed to gain an insight into its binding mode with xanthine oxidase, and to provide the basis for further structure-guided design of new non-purine xanthine oxidase inhibitors associated with the xanthone framework. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：4013 / 4015

页数：3

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