Muzychka Oksana V, Kobzar Oleksandr L, Popova Antonina V, Frasinyuk Mykhaylo S, Vovk Andriy I
Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Murmanska, 1, 02660, Kyiv 94, Ukraine.
Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Murmanska, 1, 02660, Kyiv 94, Ukraine.
Bioorg Med Chem. 2017 Jul 15;25(14):3606-3613. doi: 10.1016/j.bmc.2017.04.048. Epub 2017 May 6.
Xanthine oxidase is a potential target for treatment of hyperuricemia and gout. In this study, a number of A- and B-ring carboxylated aurone derivatives were synthesized and evaluated for their ability to inhibit xanthine oxidase in vitro. According to the results obtained, two different ranges of inhibitory activity were observed. The aurones with carboxylic acid group at the 4'-position of B-ring were found to be potent inhibitors of the enzyme with IC values in the low micromolar range. The effects of these compounds were about 50 fold higher than of A-ring modified aurones with carboxymethoxy group at the 6-position. The binding modes of the carboxylated aurones in the active site of xanthine oxidase were explained using molecular docking calculations.
黄嘌呤氧化酶是治疗高尿酸血症和痛风的一个潜在靶点。在本研究中，合成了一系列A环和B环羧化的噢哢衍生物，并对其体外抑制黄嘌呤氧化酶的能力进行了评估。根据所得结果，观察到了两种不同范围的抑制活性。发现B环4'-位带有羧酸基团的噢哢是该酶的强效抑制剂，其IC值处于低微摩尔范围内。这些化合物的效果比在6-位带有羧甲氧基的A环修饰噢哢高约50倍。使用分子对接计算解释了羧化噢哢在黄嘌呤氧化酶活性位点的结合模式。
