Conversion to purpurogallin, a key step in the mechanism of the potent xanthine oxidase inhibitory activity of pyrogallol
Conversion to purpurogallin, a key step in the mechanism of the potent xanthine oxidase inhibitory activity of pyrogallol
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DOI：
10.1016/j.freeradbiomed.2017.02.037
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发表时间：
2017-05-01
影响因子：
7.4
通讯作者：
Masuda, Toshiya
中科院分区：
文献类型：
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作者：
Honda, Sari;Fukuyama, Yuya;Masuda, Toshiya
在本研究中，研究了烘焙咖啡中发现的主要抑制剂连苯三酚的黄嘌呤氧化酶（XO）抑制活性的机制。连苯三酚不稳定，在 pH 7.4 的溶液（人体体液的生理模型）中很容易转化为红没食子素。通过比较它们的IC50值（红没食子素为0.2 μ mol L-1，邻苯三酚为1.6 p.mol L-1），可以看出所产生的红没食子素的XO抑制活性高于邻苯三酚。在 pH 7.4 溶液中预孵育可增强连苯三酚的 XO 活性。虽然4-甲基连苯三酚的初始XO抑制活性较弱(IC50 33.3 mu mol L-1)，但在pH 7.4溶液中预孵育也增强了其XO抑制活性。相比之下，5-甲基连苯三酚不能转化为相应的红没食子素衍生物，在pH 7.4溶液中孵育前后没有表现出XO抑制活性。分子对接模拟表明，紫没食子素对 XO 的亲和力比相应的连苯三酚更强。这些结果表明，在连苯三酚中看似观察到的有效 XO 抑制活性实际上源自其在碱性条件下化学转化为红没食子素。
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 IC50 values (0.2 mu mol L-1 for purpurogallin, 1.6 p.mol L-1 for 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 (IC50 33.3 mu mol L-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.