热休克蛋白(HSP)90是真核细胞中最丰富和重要的一类分子伴侣蛋白，广泛参与受体蛋白的折叠、稳定、激活和组装，已经成为目前肿瘤治疗的重要靶点，HSP90 抑制剂也成为抗肿瘤药物研究的前沿和热点之一。前期从楝科植物毛麻楝中分离得到的结构新颖的柠檬苦素具有显著的HSP90抑制作用（IC50：10-20 nM）和抗肿瘤活性(IC50:10-30μM)。本项目拟以HSP90抑制活性为指导，从有一定研究基础的三种楝科药用植物麻楝、滇红椿和割舌树中定向寻找、快速分离纯化结构新颖独特的柠檬苦素，并在此基础上深入研究抗肿瘤活性柠檬苦素与HSP90的作用位点和可能影响的主要下游客户蛋白及通路，阐明其抗肿瘤作用机制。本项目致力于从丰富的植物资源宝库中研究发现具有抗肿瘤活性、结构新颖的柠檬苦素型HSP90抑制剂并阐明其作用机制，对具有自主知识产权抗肿瘤药物的研发具有重要的学术价值和科学意义！

Heat shock protein 90 (HSP90) , the most abundant and important molecular chaperone cells, is involved in the folding, stabilization, activation and assembly of a wide range of client proteins. HSP90 has become an important target in tumor treatment, and HSP90 inhibitors have also become one of the focal and hot themes in research of the anticancer drug. It is found from our previous study that a series of novel limonoid orthoesters with antitumor effect isolated from Chukrasia tabularis var. velutina(Meliaceae) possessed a very significant HSP90 inhibitory activity (IC50:10-20 nM) and antitumor effects(IC50:10-30μM). We aim to quick screen,isolate and purify limonoid derivatives with novel structures and significant HSP90 inhibition activities from three medicinal plants rich in limonoids from the Meliaceae family, Chukrasia tabularis, Toona ciliata Roem. var. yunnanensis and Walsura robusta. Further study on the actional sites between the active compounds and HSP90 protein,the main downstream client proteins that may take affect, and the mechanism of antitumor effects. This project is committed to finding novel limonoids with potential antitumor activity based on HSP90 inhibition from the trove of botanical resources,which have great academic value and scientific significance to the research and development of antitumor drugs.