Mitomo Shunsuke, Hirota Mitsuru, Fujita Tomoyuki
a Graduate School of Science and Technology, Department of Agriculture , Shinshu University , Nagano , Japan.
Biosci Biotechnol Biochem. 2019 May;83(5):813-823. doi: 10.1080/09168451.2019.1576501. Epub 2019 Feb 7.
Excessive uric acid production, which causes gout and hyperuricemia, can be blocked by inhibiting xanthine oxidase (XO). However, some agents to block on XO often cause side effects, thereby necessitating the identification of new inhibitors. During the screening of XO inhibitors from various mushroom extracts, we found that a methanolic extract of the fruiting bodies of Tyromyces fissilis, an inedible and non-toxic fungus, showed inhibitory activity. Both n-hexane and ethyl acetate layers, obtained by partitioning this extract exhibited XO inhibitory activity. Subsequently, using an activity-guided separation method, eight active compounds (1-8) were isolated. The structures of five of the new compounds, 2-4, 6, and 7, were elucidated by spectral analysis and chemical derivatization. All compounds had a salicylic acid moiety with an aliphatic group at the C-6 position. Notably, 2-hydroxy-6-pentadecylbenzoic acid (1) showed the highest level of XO noncompetitive inhibition (58.9 ± 2.2% at 25 µM).
导致痛风和高尿酸血症的尿酸过度生成可通过抑制黄嘌呤氧化酶（XO）来阻断。然而，一些阻断XO的药物常常会引起副作用，因此需要鉴定新的抑制剂。在从各种蘑菇提取物中筛选XO抑制剂的过程中，我们发现裂拟层孔菌（一种不可食用且无毒的真菌）子实体的甲醇提取物具有抑制活性。通过对该提取物进行分配得到的正己烷层和乙酸乙酯层均表现出XO抑制活性。随后，采用活性导向分离法分离出了8种活性化合物（1 - 8）。通过光谱分析和化学衍生化确定了5种新化合物（2 - 4、6和7）的结构。所有化合物都含有一个在C - 6位带有脂肪族基团的水杨酸部分。值得注意的是，2 - 羟基 - 6 - 十五烷基苯甲酸（1）在25 μM时表现出最高水平的XO非竞争性抑制（58.9 ± 2.2%）。
