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Structure-Activity Relationships and Docking Studies of Hydroxychavicol and Its Analogs as Xanthine Oxidase
Keiji Nishiwaki1, Kanae Ohigashi1, Takahiro Deguchi1
1Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kindai University.
Abstract:
Hydroxychavicol (HC), which is obtained from the leaves of Piper betle LINN. (Piperaceae), inhibits xanthine oxidase (XO) with an IC50 value of 16.7 µM, making it more potent than the clinically used allopurinol (IC50=30.7 µM). Herein, a structure-activity relationship analysis of the polar part analogs of HC was conducted and an inhibitor was discovered with a potency 13 times that of HC. Kinetic studies have revealed that HC and its active analog inhibit XO in an uncompetitive manner. The binding structure prediction of these inhibitor molecules to the XO complex with xanthine suggested that both compounds (HC and its analog) could simultaneously form hydrogen bonds with xanthine and XO.
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