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Discovery of novel curcumin derivatives targeting xanthine oxidase and urate transporter 1 as anti-hyperuricemic agents.
Bioorg Med Chem. 2017 01 01; 25(1):166-174.BM

Abstract

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.

Authors+Show Affiliations

Department of Medicinal Chemistry, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, PR China.State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.Department of Medicinal Chemistry, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, PR China.Department of Medicinal Chemistry, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, PR China.Department of Medicinal Chemistry, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, PR China.Department of Medicinal Chemistry, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, PR China.Department of Medicinal Chemistry, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, PR China. Electronic address: huanqiuli@suda.edu.cn.State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: huqh@cpu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28340987

Citation

Ao, Gui-Zhen, et al. "Discovery of Novel Curcumin Derivatives Targeting Xanthine Oxidase and Urate Transporter 1 as Anti-hyperuricemic Agents." Bioorganic & Medicinal Chemistry, vol. 25, no. 1, 2017, pp. 166-174.
Ao GZ, Zhou MZ, Li YY, et al. Discovery of novel curcumin derivatives targeting xanthine oxidase and urate transporter 1 as anti-hyperuricemic agents. Bioorg Med Chem. 2017;25(1):166-174.
Ao, G. Z., Zhou, M. Z., Li, Y. Y., Li, S. N., Wang, H. N., Wan, Q. W., Li, H. Q., & Hu, Q. H. (2017). Discovery of novel curcumin derivatives targeting xanthine oxidase and urate transporter 1 as anti-hyperuricemic agents. Bioorganic & Medicinal Chemistry, 25(1), 166-174. https://doi.org/10.1016/j.bmc.2016.10.022
Ao GZ, et al. Discovery of Novel Curcumin Derivatives Targeting Xanthine Oxidase and Urate Transporter 1 as Anti-hyperuricemic Agents. Bioorg Med Chem. 2017 01 1;25(1):166-174. PubMed PMID: 28340987.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discovery of novel curcumin derivatives targeting xanthine oxidase and urate transporter 1 as anti-hyperuricemic agents. AU - Ao,Gui-Zhen, AU - Zhou,Meng-Ze, AU - Li,Yu-Yao, AU - Li,Si-Ning, AU - Wang,Hua-Nian, AU - Wan,Qian-Wen, AU - Li,Huan-Qiu, AU - Hu,Qing-Hua, Y1 - 2016/10/20/ PY - 2016/09/05/received PY - 2016/10/17/revised PY - 2016/10/18/accepted PY - 2017/3/26/entrez PY - 2017/3/28/pubmed PY - 2017/7/27/medline KW - Anti-hyperuricemic KW - Curcumin derivatives KW - Urate transporter 1 KW - Uricosuric KW - Xanthine oxidase SP - 166 EP - 174 JF - Bioorganic & medicinal chemistry JO - Bioorg. Med. Chem. VL - 25 IS - 1 N2 - 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. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/28340987/Discovery_of_novel_curcumin_derivatives_targeting_xanthine_oxidase_and_urate_transporter_1_as_anti_hyperuricemic_agents_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(16)31015-X DB - PRIME DP - Unbound Medicine ER -