Virtual and In Vitro Bioassay Screening of Phytochemical Inhibitors from Flavonoids and Isoflavones Against Xanthine Oxidase and Cyclooxygenase-2 for Gout Treatment

Authors

  • Yadi Li,

    Corresponding author
    1. Lunan Pharmaceutical Group Shandong New Time Pharmaceutical Co., Ltd, Feixian, Shandong, China
    • Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, China
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  • Christopher M. Frenz,

    1. Department of Computer Engineering Technology, New York City College of Technology (CUNY), Brooklyn, NY, USA
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  • Zhiwen Li,

    1. Lunan Pharmaceutical Group Shandong New Time Pharmaceutical Co., Ltd, Feixian, Shandong, China
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  • Mianhua Chen,

    1. Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, China
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  • Yurong Wang,

    1. Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, China
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  • Fengjuan Li,

    1. Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, China
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  • Cheng Luo,

    1. Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, China
    2. Department of Biotechnology, University of Tartu, Tartu, Estonia
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  • Jian Sun,

    1. Department of Chemistry, University of Hong Kong, Hong Kong, China
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  • Lars bohlin,

    1. Department of Medicinal Chemistry, University of Uppsala, Uppsala, Sweden
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  • Zhenjing Li,

    1. Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, China
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  • Hua Yang,

    1. Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, China
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  • Changlu Wang

    Corresponding author
    1. Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, China
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Corresponding authors: Changlu Wang, changluwang@yahoo.com.cn and Yadi Li, leeyadi@163.com

Abstract

Synthetic drugs such as allopurinol and benzbromarone 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 and cyclooxygenase-2 enzymes. In this study, we report the screening of nine compounds of flavonoids from the ZINC and PubChem databases (containing 2092 flavonoids) using the igemdock software tool against the xanthine oxidase and cyclooxygenase-2 3D protein structures. Each compound was also evaluated by an in vitro bioassay testing the inhibition of xanthine oxidase and cyclooxygenase-2. Myricetin and luteolin were found to be the potential dual inhibitors of xanthine oxidase and cyclooxygenase-2 as demonstrated by IC50: 62.7 and 3.29 μg/mL (xanthine oxidase)/70.8 and 16.38 μg/mL (cyclooxygenase-2), respectively. In addition, structure–activity relationships and other important factors of the flavonoids binding to the active site of xanthine oxidase and cyclooxygenase-2 were discussed, which is expected for further rational drug design.

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