新骨架重要活性天然分子的发现与功能研究

本项目拟采用基于药用植物生源途径和结构双导向的新骨架天然活性化合物发现与研究的策略，不同于生物活性导向的研究，本策略既能显著提高发现新骨架结构的效率，也保证了发现活性化合物的几率（由于基于药用植物）。首先通过生源途径和结构双导向分析研究，从大量中草药中选定20种含有新颖结构的品种；再利用现代分离技术、波谱学、化学、药物筛选和药理学相结合对其进行深入的研究，旨在发现具有免疫抑制等活性的新类型和新骨架的化合物；对重要活性物质进行系统的结构修饰、构效关系和功能研究，最终以期发现药物先导或药物候选。研究的预期目标包括：1）获得各类化合物350-400个，其中新结构150-200个，新骨架类型的化合物15-20个；2）发现具有重要生物活性的化合物20-25个，获得药物先导化合物或药物候选1-3个，并希望能够以此阐明部分药用植物的药效物质基础；3）研究结果将在重要国际杂志上发表研究论文或申请专利。

We will conduct this project to explore the biological properties, especially the immunosuppressive activity, and the underlying potential of medical application of the compounds isolated from Chinese medicinal plants, which contains structurally diverse and novel compounds based on our strategy of the biosynthesis and structure directed analysis. Our strategy is different from the bioactivity guided isolation, it not only provides a big opportunity to find compounds with new carbon skeletons, but also give high rates to hit biological compounds due to the study is based on medicinal plants. The research objectives are including: To finish the chemical study and biological tests, in particular the tests of immunosuppressive activity on 20 Chinese medicinal herbs selected to contain structurally diverse and novel compounds from a big number of TCM plants. The accomplishment of this project will lead to the isolation of 350 to 400 structurally diverse compounds, including 150 to 200 new structures, of which 15 to 20 compounds will possess new carbon skeletons; and identification 20 to 25 biologically important components. Structural modification, structure-activity relationship and an in-depth pharmaceutical study on the biologically important compounds identified in the project will be carried out, and 1 to 3 drug leads or drug candidates will be hopefully afforded subsequently. The research results will publish research papers in the international top journals, and apply patents. In addition. a number of PhD students and some of the young scientists will be trained from the successful completion of this project.