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

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• 作者：Gui-Zhen Ao^a ; Meng-Ze Zhou^b ; Yu-Yao Li^a ; Si-Ning Li^a ; Hua-Nian Wang^a ; Qian-Wen Wan^a ; Huan-Qiu Li^a ; ^{huanqiuli@suda.edu.cn} ; Qing-Hua Hu^b ; ^{huqh@cpu.edu.cn}
• 关键词：Xanthine oxidase ; Urate transporter 1 ; Anti-hyperuricemic ; Uricosuric ; Curcumin derivatives
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：1 January 2017
• 年：2017
• 卷：25
• 期：1
• 页码：166-174
• 全文大小：842 K
• 卷排序：25

文摘

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.