耐药性和毒副作用是目前治疗艾滋病临床用药最为严重的问题。从传统中药、植物和真菌资源中寻找新的抗HIV药物或先导化合物，是国内外新药研制中非常活跃的领域。申请者发现大戟属植物火殃簕和金刚纂3个极性部位具有显著的抗HIV活性，活性导向分离获得活性部位和4个活性程度不等的阿替生烷型二萜。本项目将: (1) 选择3种大戟属植物（火殃簕、金刚篆和霸王鞭）进行系统的化学成分研究，评价分离得到化合物的抗HIV活性；(2) 分析活性化合物在3种植物中的含量和分布特点，从大戟属近缘植物中深入挖掘含有抗艾滋病毒活性的二萜药物新资源；(3) 对前期工作中发现的量大的活性化合物进行结构修饰研究。(4) 在活性化合物分离和结构修饰的研究基础上，探讨阿替生烷型二萜抗HIV的构效关系，并对高活性化合物的抗HIV作用机理进行研究，为火殃簕及其近缘植物的开发利用与抗HIV活性先导化合物的发现奠定基础

The multidrug resistance and side effect are the most serious problem for the treatment of HIV infection. It is essential to continue to develop new antiretroviral drugs with potency against an ever-wider range of viral mutants including those which engender resistance to multidrug classes, and natural products from medicinal plant and fungi are important sources of new drugs. As part of a search for anti-HIV agents of natural origin, a bioactive investigation of 23 medicinal plants and 347 pure compounds were studied to ascertain their potential anti-HIV activity. As a result, three crude extracts of Euphorbia antiquorum and E. royleana were found to significantly inhibit HIV-1. Bioassay-guided phytochemical investigation resulted in the isolation of one bioactive extract and four atisen-type diterpenoids with anti-HIV activities. Based on our preliminary research, the current project will include: (1) The phytochemical investigation of the chemical constituents of E. antiquorum, E. neriifolia and E. royleana in order to isolate more diterpenoids as anti-HIV leading compounds. We will use an X4 virus NL4-3 and an R5 virus HIV-1 BaL for initial evaluation of the anti-HIV activity of the proposed plant extracts and pure compounds in CEM-CCR5 cells. (2) The analysis of the content and distribution of these active compounds in the above 3 plants, and the search for abailable resources containing these anti-HIV diterpenoids from the other related plants of the genus Euphorbia. (3) The structural modification study on biactive compound which has large quantity and was identified as an main anti-HIV principle of E. antiquorum. (4) The anti-HIV bioactive evaluation of the corresponding atisane derivatives and the summarization of their structure-activity relationship. Based on the above work, the initial determination of mechanisms of action of the most active compound will be conducted. This study will provide solid scientific evidence for the exploitation of E. antiquorum and its related plants, as well as the development of new anti-AIDS drugs.