title: Virtual and in vitro bioassay screening of phytochemical inhibitors from flavonoids and isoflavones against xanthine oxidase and cyclooxygenase-2 for gout treatment.
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 IC(50): 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.
authors.forename: Yadi
authors.initials: Y
authors.lastname: Li
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Frenz
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Li
authors.forename: Mianhua
authors.initials: M
authors.lastname: Chen
authors.forename: Yurong
authors.initials: Y
authors.lastname: Wang
authors.forename: Fengjuan
authors.initials: F
authors.lastname: Li
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Lars
authors.initials: L
authors.lastname: bohlin
authors.forename: Zhenjing
authors.initials: Z
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.forename: Changlu
authors.initials: C
authors.lastname: Wang
mesh_terms: D001665:Binding Sites; D001681:Biological Assay; D051546:Cyclooxygenase 2 / Q000737:chemistry* / Q000378:metabolism; D062126:Databases, Chemical; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D005419:Flavonoids / Q000737:chemistry* / Q000627:therapeutic use; D006073:Gout / Q000188:drug therapy; D006801:Humans; D007529:Isoflavones / Q000737:chemistry* / Q000627:therapeutic use; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D012984:Software; D013329:Structure-Activity Relationship; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D007529:Isoflavones; D051546:Cyclooxygenase 2; D014969:Xanthine Oxidase