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. 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. Lunan Pharmaceutical Group Shandong New Time Pharmaceutical co., ltd
      Corresponding author
      Changlu Wang, Professor
      College of Food Engineering and Biotechnology
      Tianjin University of Science and Technology
      No. 1038 Dagu Nan Road, Hexi District, Tianjin 300222
      P. R.. China
      Yadi Li
      Lunan Pharmaceutical Group Shandong New Time Pharmaceutical co., ltd
      No.1 North Outer Ring Road, Feixian County 273400
      Shandong Province, China
      Tel: 86-22-6027-2219(O), Fax : 86-22-2811-8424
      E-MAIL: changluwang@yahoo.com.cn; leeyadi@163.com
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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
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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, 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, 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
      Corresponding author
      Changlu Wang, Professor
      College of Food Engineering and Biotechnology
      Tianjin University of Science and Technology
      No. 1038 Dagu Nan Road, Hexi District, Tianjin 300222
      P. R.. China
      Yadi Li
      Lunan Pharmaceutical Group Shandong New Time Pharmaceutical co., ltd
      No.1 North Outer Ring Road, Feixian County 273400
      Shandong Province, China
      Tel: 86-22-6027-2219(O), Fax : 86-22-2811-8424
      E-MAIL: changluwang@yahoo.com.cn; leeyadi@163.com
    Search for more papers by this author

Corresponding author
Changlu Wang, Professor
College of Food Engineering and Biotechnology
Tianjin University of Science and Technology
No. 1038 Dagu Nan Road, Hexi District, Tianjin 300222
P. R.. China
Yadi Li
Lunan Pharmaceutical Group Shandong New Time Pharmaceutical co., ltd
No.1 North Outer Ring Road, Feixian County 273400
Shandong Province, China
Tel: 86-22-6027-2219(O), Fax : 86-22-2811-8424
E-MAIL: changluwang@yahoo.com.cn; leeyadi@163.com

Abstract:

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.

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