五倍子非单宁抗HIV活性成分研究

Approved drugs for HIV facing the challenge of violent side-effect, drug resistance and drug induced HIV mutations et al., discovering of drugs for HIV from natural source through target-guide identification of new bioactive molecules for HIV is one of the most effective methods. As a unique traditional Chinese medicine, Chinese gallnut is the gall originated from the abnormal growth of the Rhus leaf tissue in response to secretion of parasitic aphids (family Pemphigidae). Chinese gallnut posses diversified activity including anti-HIV. But until presently, people know little about the bioactive constituents other than tannins in Chinese gallnut. With 5000-7000 tons production of Chinese gallnut per year in China, to find some bioactive molecules in the gallnut is to find a large treasury. Systematic study on the non-tannic constituents in Chinese gallnut by us has lead to identifying 13 compounds in it, among which, betulinic acid and betulonic acid possess anti-HIV activity, and the two molecules can be translated into 3-O-(3＇, 3＇-dimethylsuccinyl) betulinic acid with new active mechanism by targeting the HIV capsid protein p25 and disrupt the cleavage of p25 to mature p24. The molecule is potent to be a HIV inhibitor and has been in phase II clinic study. This program will purify and identify chemical constituents from 4 kinds of Chinese gallnuts by isolating the compounds with chromatography, identifying the constituents by 1D-, 2D-NMR, UV, IR, and X-ray crystallography and combined with anti-HIV bioactivity screen, thus to find potent anti-HIV molecule or lead compounds.

当前治疗艾滋病的药物面临毒副作用和抗药性等重大挑战，通过细胞毒活性和靶向机制从天然产物中发现新活性分子是抗HIV药物发现的重要方法。五倍子是我国的传统中药，是昆虫和植物相互作用的独特产物。五倍子有包括抗HIV在内的多种药理活性，是发现抗HIV活性分子和药物先导的宝贵资源，但目前人们对五倍子非单宁成分的研究还处于较宏观的层面。我们首次从五倍子中发现了白桦脂醇、白桦脂酸、桦木酮酸等化合物，这三者都可以转化为一种高活性的抗HIV分子，该分子阻止HIV衣壳蛋白前体p25被剪切为成熟衣壳p24，是有潜力的抗HIV候选药物。本项目将以4种五倍子为研究对象，以树脂、正、反向硅胶、凝胶等分离材料和常压、中压、高压柱色谱分离、纯化单体化合物，以1D-，2D-NMR、MS、UV、IR、X-射线衍射等谱学方法确定化合物的分子结构，结合抗HIV活性评价和构效关系研究，以期从五倍子中发现抗HIV活性分子和药物先导。

当前治疗艾滋病的药物面临毒副作用和抗药性等重大挑战，通过细胞毒活性和靶向机制从天然产物中发现新活性分子是抗HIV药物发现的重要方法。五倍子是我国的传统中药，是昆虫和植物相互作用的独特产物。五倍子有包括抗HIV在内的多种药理活性，是发现抗HIV活性分子和药物先导的宝贵资源，但目前人们对五倍子非单宁成分的研究还处于较宏观的层面。本项目将以4种五倍子（角倍Schlechtendalia chinensis、肚倍Kaburagia rhusicola、倍花Nurudea shiraii、铁倍花Floraphis meitanensis）为研究对象，以树脂、正、反向硅胶、凝胶等分离材料和常压、中压、高压柱色谱分离、纯化单体化合物，以1D-，2D-NMR、MS、UV、IR、X-射线衍射等谱学方法确定化合物的分子结构，结合抗HIV活性评价和构效关系研究，以期从五倍子中发现抗HIV活性分子和药物先导。