title: Conversion to purpurogallin, a key step in the mechanism of the potent xanthine oxidase inhibitory activity of pyrogallol.
abstract: In this study, the mechanism of the xanthine oxidase (XO) inhibitory activity of pyrogallol, the main inhibitor found in roasted coffee, was investigated. Pyrogallol was unstable and readily converted to purpurogallin in a pH 7.4 solution, a physiological model of human body fluids. The XO inhibitory activity of the produced purpurogallin was higher than that of pyrogallol, as evidenced by comparing their IC50values (0.2µmolL-1for purpurogallin, 1.6µmolL-1for pyrogallol). The XO activity of pyrogallol was enhanced by pre-incubation in pH 7.4 solution. Although the initial XO inhibitory activity of 4-methylpyrogallol was weak (IC5033.3µmolL-1), its XO inhibitory activity was also enhanced by pre-incubation in the pH 7.4 solution. In contrast, 5-methylpyrogallol, which could not be transformed into corresponding purpurogallin derivatives, did not show XO inhibitory activity before or after incubation in pH 7.4 solution. Molecular docking simulations clarified that purpurogallins have stronger affinities for XO than corresponding pyrogallols. These results revealed that the potent XO inhibitory activity seemingly observed in pyrogallol is actually derived from its chemical conversion, under alkaline conditions, into purpurogallin.
authors.affiliation: Graduate School of Human Life Science, Osaka City University, Osaka 558-8585, Japan.
authors.forename: Sari
authors.initials: S
authors.lastname: Honda
authors.affiliation: Graduate School of Human Life Science, Osaka City University, Osaka 558-8585, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Fukuyama
authors.affiliation: Graduate School of Agriculture, Ehime University, Matsuyama 790-8566, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Nishiwaki
authors.affiliation: Faculty of Human Life Science, Shikoku University, Tokushima 771-1192, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Masuda
authors.affiliation: Graduate School of Human Life Science, Osaka City University, Osaka 558-8585, Japan. Electronic address: masuda_t@life.osaka-cu.ac.jp.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Masuda
mesh_terms: D000493:Allopurinol; D001567:Benzocycloheptenes / Q000737:chemistry* / Q000378:metabolism; D003069:Coffee / Q000737:chemistry; D006801:Humans; D062105:Molecular Docking Simulation; D010084:Oxidation-Reduction; D011748:Pyrogallol / Q000737:chemistry / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: D001567:Benzocycloheptenes; D003069:Coffee; D011748:Pyrogallol; D000493:Allopurinol; D014969:Xanthine Oxidase; C026133:purpurogallin
keywords: Chemical mechanism; Physiological pH; Purpurogallin; Pyrogallol; Xanthine oxidase inhibition