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  3. Old drug, new indication: Olsalazine sodium reduced serum uric acid levels in mice via inhibiting xanthine oxidoreductase activity

Old drug, new indication: Olsalazine sodium reduced serum uric acid levels in mice via inhibiting xanthine oxidoreductase activity

  • J Pharmacol Sci. 2017 Nov;135(3):114-120. doi: 10.1016/j.jphs.2017.10.007.
Yanfen Niu 1,  Hongjian Li 2,  Lihui Gao 3,  Hua Lin 3,  Hsiangfu Kung 4,  Marie Chia-Mi Lin 5,  Kwong-Sak Leung 6,  Man-Hon Wong 7,  Wenyong Xiong 8,  Ling Li 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China; Biomedical Engineering Research Center, Kunming Medical University, Kunming, 650500, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
  • 2 Institute of Future Cities, Chinese University of Hong Kong, Hong Kong, China; Department of Computer Science and Engineering, Chinese University of Hong Kong, Hong Kong, China.
  • 3 Biomedical Engineering Research Center, Kunming Medical University, Kunming, 650500, PR China.
  • 4 Biomedical Engineering Research Center, Kunming Medical University, Kunming, 650500, PR China; School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China.
  • 5 Biomedical Engineering Research Center, Kunming Medical University, Kunming, 650500, PR China; Shenzhen Key Lab of Translational Medicine of Tumor, School of Medicine, Shenzhen University, Shenzhen, PR China.
  • 6 Department of Computer Science and Engineering, Chinese University of Hong Kong, Hong Kong, China; Institute of Future Cities, Chinese University of Hong Kong, Hong Kong, China.
  • 7 Department of Computer Science and Engineering, Chinese University of Hong Kong, Hong Kong, China.
  • 8 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China. Electronic address: xiong.wenyong@mail.kib.ac.cn.
  • 9 Biomedical Engineering Research Center, Kunming Medical University, Kunming, 650500, PR China. Electronic address: kmli62@163.com.
PMID: 29132796 DOI: 10.1016/j.jphs.2017.10.007
Abstract

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.

Keywords

Hyperuricemia; Olsalazine sodium; Uric acid; Xanthine oxidase.

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