title: Identification of a potent xanthine oxidase inhibitor from oxidation of caffeic acid.
abstract: Inhibitory activity of Fe-ion-catalyzed radical oxidation products from 22 types of phenolic compounds toward xanthine oxidase (XO) was investigated. Phenols are readily oxidizable compounds in nature and, thus, showed potent antioxidant activities. Among the phenols screened in this study, noticeable activity was observed in the oxidation product of caffeic acid, whereas almost no XO-inhibitory activity of caffeic acid was observed. Assay-guided purification of the oxidation product of caffeic acid afforded a highly potent XO inhibitor, with an IC50 value that was calculated to be 60 nmol L(-1), which indicated XO-inhibitory activity much stronger than that of allopurinol (IC50 = 1 μmol L(-1)), a potent XO inhibitor and excellent medicine for the treatment of gout. The chemical structure of this new XO inhibitor was investigated by one- and two-dimensional NMR and HR-ESI-MS analyses, and the unique tetracyclic structure was confirmed by synthesis starting from commercially available 1,2,4-trimethoxybenzene and 3,4-dimethoxylbenzoyl chloride.
authors: Graduate School of Integrated Arts and Sciences, University of Tokushima, Tokushima 770-8502, Japan. Electronic address: masuda.ias@tokushima-u.ac.jp.
authors: Toshiya
authors: T
authors: Masuda
authors: Graduate School of Integrated Arts and Sciences, University of Tokushima, Tokushima 770-8502, Japan.
authors: Yoshimi
authors: Y
authors: Shingai
authors: Graduate School of Integrated Arts and Sciences, University of Tokushima, Tokushima 770-8502, Japan.
authors: Chizuru
authors: C
authors: Takahashi
authors: Graduate School of Integrated Arts and Sciences, University of Tokushima, Tokushima 770-8502, Japan.
authors: Miyuki
authors: M
authors: Inai
authors: Graduate School of Integrated Arts and Sciences, University of Tokushima, Tokushima 770-8502, Japan.
authors: Yukari
authors: Y
authors: Miura
authors: Graduate School of Integrated Arts and Sciences, University of Tokushima, Tokushima 770-8502, Japan.
authors: Sari
authors: S
authors: Honda
authors: Faculty of Human Life Science, Shikoku University, Tokushima 771-1192, Japan.
authors: Akiko
authors: A
authors: Masuda
mesh_terms: D000493:Allopurinol / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D002109:Caffeic Acids / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D007501:Iron / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010636:Phenols / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D017382:Reactive Oxygen Species; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000975:Antioxidants; D002109:Caffeic Acids; D004791:Enzyme Inhibitors; D010636:Phenols; D017382:Reactive Oxygen Species; D000493:Allopurinol; D007501:Iron; D014969:Xanthine Oxidase; C040048:caffeic acid
keywords: Antioxidant; Caffeic acid; Free radicals; Polyphenol oxidation; Structure determination; Xanthine oxidase inhibitor