中草药有效成分化合物与黄嘌呤氧化酶的分子对接及药物特性研究

Molecular docking and ADMET studies on traditional Chinese medicines' ingredients and xanthine oxidase

运用Surflex-Dock和.FAF-Drugs2对5种能治疗高尿酸血症的中草药的65个成分与黄嘌呤氧化酶(简称XO)进行柔性分子对接和ADMET预测研究,并分析它们在XO的活性位点的结合模式。结果显示当中的51个化合物有比常用西药别嘌呤醇更佳的打分函数和更稳定的结合模式。其中以花旗松素-3-O-α-L-鼠李糖苷、阿斯特酚苷和虎杖甙的打分函数最高,它们亦被预测为有良好的口服药物特性,可用于研发新型黄嘌呤氧化酶抑制剂。

Xanthine oxidase （EC 1.17.3.2） is an important purine metabolizing enzyme, it catalyzes xanthine and hypoxanthine to uric acid by oxidation reactions. Inhibition of this enzyme prevents and treats hyperuricemia, leading to reduced risk of certain diseases such as gout and kidney stones. Studies showed xanthine oxidase inhibitors can reduce free radicals formation and prevent damage of a variety of cells, reducing the risk of Alzheimer＇s disease, kidney disease and fibrosis. However, most of these inhibitors have different level of side effects, which has limited their usage. Currently, the world＇s population in suffering hyperuricemia is highly significant, approximately 5 to 30%. Therefore a new effective inhibitor with limited side-effects is necessary. In this study, molecular docking and ADMET predictions were performed on 65 active ingredients in five commonly used antihyperuricemic traditional Chinese medicines using Surflex-Dock and FAF-Drugs2. The results indicate 51 constituents of the five herbs have advanced binding scores than the gold standard antihyperuricemic agents, allopurinol. This study reports taxifolin-3-o-alpha-l-rhamnoside, astringin and polydatin have the highest prospective to be formulated as xanthine oxidase inhibitors since they have high predicted binding scores and acceptable ADMET properties.