Old drug, new indication: Olsalazine sodium reduced serum uric acid levels in mice via inhibiting xanthine oxidoreductase activity
Niu, Yanfen1,3,7; Li, Hongjian2,4; Gao, Lihui3; Lin, Hua3; Kung, Hsiangfu3,5; Lin, Marie Chia-mi3,6; Leung, Kwong-Sak2,4; Wong, Man-Hon4; Xiong, Wenyong1; Li, Ling3
2017-11-01
发表期刊JOURNAL OF PHARMACOLOGICAL SCIENCES
ISSN1347-8613
卷号135期号:3页码:114-120
摘要Hyperuricemia, a long-term purine metabolic disorder, is a well-known risk factor for gout, hypertension and diabetes. In maintaining normal whole-body purine levels, xanthine oxidase (XOD) is a key enzyme in the purine metabolic pathway, as it catalyzes the oxidation of hypoxanthine to xanthine and finally to uric acid. Here we used the protein-ligand docking software idock to virtually screen potential XOD inhibitors from 3167 approved small compounds/drugs. The inhibitory activities of the ten compounds with the highest scores were tested on XOD in vitro. Interestingly, all the ten compounds inhibited the activity of XOD at certain degrees. Particularly, the anti-ulcerative-colitis drug olsalazine sodium demonstrated a great inhibitory activity for XOD (IC50 = 3.4 mg/L). Enzymatic kinetic studies revealed that the drug was a hybrid-type inhibitor of xanthine oxidase. Furthermore, the drug strikingly decreased serum urate levels, serum/hepatic activities of XOD at a dose-dependent manner in vivo. Thus, we demonstrated a successful hunting process of compounds/drugs for hyperuricemia through virtual screening, supporting a potential usage of olsalazine sodium in the treatment of hyperuricemia. (c) 2017 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.
关键词Olsalazine Sodium Hyperuricemia Xanthine Oxidase Uric Acid
DOI10.1016/j.jphs.2017.10.007
语种英语
WOS记录号WOS:000418237700003
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/60477
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
2.Chinese Univ Hong Kong, Inst Future Cities, Hong Kong, Hong Kong, Peoples R China
3.Kunming Med Univ, Biomed Engn Res Ctr, 1168 Western Chunrong Rd,Yuhua St, Kunming 650500, Yunnan, Peoples R China
4.Chinese Univ Hong Kong, Dept Comp Sci & Engn, Hong Kong, Hong Kong, Peoples R China
5.Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China
6.Shenzhen Univ, Sch Med, Shenzhen Key Lab Translat Med Tumor, Shenzhen, Peoples R China
7.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
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Niu, Yanfen,Li, Hongjian,Gao, Lihui,et al. Old drug, new indication: Olsalazine sodium reduced serum uric acid levels in mice via inhibiting xanthine oxidoreductase activity[J]. JOURNAL OF PHARMACOLOGICAL SCIENCES,2017,135(3):114-120.
APA Niu, Yanfen.,Li, Hongjian.,Gao, Lihui.,Lin, Hua.,Kung, Hsiangfu.,...&Li, Ling.(2017).Old drug, new indication: Olsalazine sodium reduced serum uric acid levels in mice via inhibiting xanthine oxidoreductase activity.JOURNAL OF PHARMACOLOGICAL SCIENCES,135(3),114-120.
MLA Niu, Yanfen,et al."Old drug, new indication: Olsalazine sodium reduced serum uric acid levels in mice via inhibiting xanthine oxidoreductase activity".JOURNAL OF PHARMACOLOGICAL SCIENCES 135.3(2017):114-120.
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