Virtual and In vitro bioassay screening of phytochemical inhibitors from flavonoids and isoflavones against Xanthine oxidase and Cyclooxygenase-2 for gout treatment

• Published in: Chemical biology & drug design 2013-04, Vol.81 (4), p.no-no
• Main Authors: Li, Yadi, Frenz, Christopher M., Li, Zhiwen, Chen, Mianhua, Wang, Yurong, Li, Fengjuan, Luo, Cheng, Sun, Jian, bohlin, Lars, Li, Zhenjing, Yang, Hua, Wang, Changlu
• Format: Article
• Language: English
• Subjects: Farmakognosi; Pharmacognosy
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/j.1747-0285.2011.01248.x

Synthetic drugs such as allopurinol and benzbroarone are commonly used to treat the complex pathogenesis of gout, a metabolic disease that results from an inflammation of the joints caused by precipitation of uric acid. We seek to discover novel phytochemicals that could treat gout, by targeting the xanthine oxidase (XO) and cyclooxygenase 2 (COX-2) enzymes. In this study, we report the screening of 9 compounds of flavonoids from the ZINC and PubChem databases (containing 2,092 flavonoids) using the iGEMDOCK software tool against the XO and COX-2 3D protein structures. Each compound was also evaluated by an in vitro bioassay testing the inhibition of XO and COX-2. Myricetin and luteolin were found to be the potential dual inhibitors of XO and COX-2 as demonstrated by IC50: 62.7 and 3.29μg/mL (XO) / 70.8 and 16.38μg/mL (COX-2), respectively. In addition, structure activity relationships and other important factors of the flavonoids binding to the active site of XO and COX-2 were discussed, which is expected for further rational drug design.