越南槐根的抗HIV活性成分研究

Chemical Constituents with Anti-HIV Activities from the Roots of Sophora tonkinensis

摘要:

为研究越南槐(Sophora tonkinensis)根的抗HIV蛋白酶活性成分及其分子对接机制，采用硅胶、MCI、Sephadex LH-20等多种色谱分离方法，对越南槐根的化学成分进行分离，采用HIV蛋白酶对化合物进行体外抗HIV活性筛选，运用分子对接手段初步探究活性化合物与HIV-1蛋白酶的结合机制。结果表明，从越南槐中共分离得到8个化合物，根据波谱数据分别鉴定为三叶豆紫檀苷(1)、苦参碱(2)、N-acetylnicotinamide (3)、2′-O-甲基腺苷(4)、毛蕊异黄酮苷(5)、玫瑰花苷(6)、环广豆根素(7)、芒柄花苷(8)，此外还分离得到塑化剂衍生物邻苯二甲酸二(2-乙基)己酯(9)和邻苯二甲酸二异丁酯(10)。抗HIV蛋白酶活性测试显示化合物1和2的IC₅₀分别为13.2和38.6 μg/mL，分子对接表明其与HIV蛋白酶有一定的结合作用。化合物3~5为首次从该植物中分离得到，化合物1和2显示中等的抗HIV蛋白酶活性。

Abstract:

In order to study the anti-HIV protease activity and molecular docking mechanism of Sophora tonkinensis roots, the chemical constituents from roots were isolated by silica gel, MCI and Sephadex LH-20. HIV protease was used to screen the compounds against HIV in vitro, and molecular docking was used to preliminarily explore the binding mechanism between the active compounds and HIV-1 protease. The results showed that eight compounds were isolated from S. tonkinensis roots. Based on spectral data, their structures were identified as trifolirhizin (1), matrine (2), N-acetylnicotinamide (3), 2'-O-methyladenosine (4), calycosin-7-O-β-D-glucoside (5), roseoside (6), sophoranochromene (7), and ononin (8). Besides, two plasticizer derivatives were also obtained as bis(2-ethylhexyl)benzene-1,2-dicarboxylate (9) and disobutyl phthalate (10). The IC₅₀ values of compounds 1 and 2 are 13.2 and 38.6 μg/mL, respectively. Molecular docking showed that it had certain binding effect with HIV protease. Compounds 3- 5 were isolated from this plant for the first time, while compounds 1 and 2 exhibited moderate anti-HIV activities.