Discovery of novel curcumin derivatives targeting xanthine oxidase and urate transporter 1 as anti-hyperuricemic agents

被引：54

作者：

Ao, Gui-Zhen ^{[1
]}

Zhou, Meng-Ze ^{[2
]}

Li, Yu-Yao ^{[1
]}

Li, Si-Ning ^{[1
]}

Wang, Hua-Nian ^{[1
]}

Wan, Qian-Wen ^{[1
]}

Li, Huan-Qiu ^{[1
]}

Hu, Qing-Hua ^{[2
]}

机构：

[1] Soochow Univ, Dept Med Chem, Coll Pharmaceut Sci, Suzhou 215123, Peoples R China

[2] China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2017年 / 25卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Xanthine oxidase; Urate transporter 1; Anti-hyperuricemic; Uricosuric; Curcumin derivatives; ANTIOXIDANT ACTIVITY; INHIBITORS; GOUT;

D O I：

10.1016/j.bmc.2016.10.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

A series of curcumin derivatives as potent dual inhibitors of xanthine oxidase (XOD) and urate transporter 1 (URAT1) was discovered as anti-hyperuricemic agents. These compounds proved efficient effects on anti-hyperuricemic activity and uricosuric activity in vivo. More importantly, some of them exhibited proved efficient effects on inhibiting XOD activity and suppressing uptake of uric acid via URAT1 in vitro. Especially, the treatment of 4d was demonstrated to improve uric acid over-production and under-excretion in oxonate-induced hyperuricemic mice through regulating XOD activity and URAT1 expression. Docking study was performed to elucidate the potent XOD inhibition of 4d. Compound 4d may serve as a tool compound for further design of anti-hyperuricemic drugs targeting both XOD and URAT1. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：166 / 174

页数：9

共 24 条

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