基于药物靶点的苗药榜佳腔皂苷元和三萜衍生物抗艾滋病活性研究

艾滋病病毒蛋白酶(HIV-1 PR)已被公认为研究艾滋病药物的靶标。我们前期研究发现含2,2-二甲基琥珀酸(DMS)结构、A环裂环(SDA)三萜化合物、常春藤皂苷元和齐墩果酸具有较好的抗HIV-1 PR活性。计算机辅助研究发现，三萜类化合物3-羟基引入羧酸半酯结构或增加含氢键官能团，抗HIV作用增强。临床上苗药榜佳腔(Lonicera fulvotomentosa Hsu)具有清热解毒和抗艾滋病作用，但化学成分复杂，抗HIV药效物质不明确，影响了其深层次的应用与开发。本研究通过现代合成技术，结合多靶点，从水解产物、衍生物合成、药理活性以及构效关系四个层次，揭示苗药榜佳皂苷元和三萜衍生物抗HIV-1 PR活性，阐明榜佳腔皂苷元及三萜衍生物抗艾滋病病毒的关系，为从民族药中开发非肽类抗艾滋病药物提供科学依据。

HIV-1 protease (HIV PR) plays an important role in the maturation of the infectious virus, and has been used as a promising target for screening anti-HIV drugs..Previously, our research results showed that some triterpenes and derivatives containing with mono- or di-2,2-dimethylsuccinic acid (DMS) or 2,3-seco-2,3-dioc acid (SDA) function group， hederagenin and oleanolic acid showed potent inhibitory activity against HIV Protease. A computer modeling study has predicted that esterification of the 3-OH of triterpene with dicarboxylic acid could improve their binding with HIV-1 PR. Lonicera fulvotomentosa Hsu, a Miao enthnic medicine, was used in clinical trial with the actions of clearing heat and removing toxin, anti HIV and regulating immune function. Since its chemical constituents are complex and bioactive components are not clear, the application and development of this herb medicine are not widely used as anti HIV agent..To investigate and develop the potent non-peptide HIV PR inhibitors from enthnic medicines, the present experiment was designed to find the inhibitory effects of hydrolysates of Lonicera fulvotomentosa and triterpene derivatives with the 2,3-seco-2,3-dioc acid , 3-O-acyl , 3,23-O-diacyl, 23-O-acyl-2,3-seco-2,3-dioic acid chain and triterpene - AZT conjugates on HIV-1 PR. The classical synthesis methods and four targets were used. This project will provide some scientific information for developing non-peptide inhibitors from enthnic medicines with hydrolysates, derivatives, pharmacological activity and structure-activity-relationships.