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


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.
著者Yanfen Niu, Hongjian Li, Lihui Gao, Hua Lin, Hsiangfu Kung, Marie Chia-mi Lin, Kwong-Sak Leung, Man-Hon Wong, Wenyong Xiong, Ling Li
期刊名稱Journal of Pharmacological Sciences
出版社Elsevier: Creative Commons Attribution Non-Commercial No-Derivatives License / Elsevier
頁次114 - 120
關鍵詞Olsalazine sodium, Hyperuricemia, Xanthine oxidase, Uric acid

上次更新時間 2020-10-10 於 01:15