抗肿瘤粗榧烷二萜的发现与研究

天然产物是发现抗肿瘤药物的重要资源，在目前临床应用的抗肿瘤药物中，约有70%与之有关。我国三尖杉属植物资源丰富，分布广泛。该属植物中罕见的粗榧烷二萜对多种肿瘤细胞具有很强抑制作用。近期，我们对该属部分植物进行了研究，发现了大量该类新二萜化合物，多个二萜显示很强的抗肿瘤活性；特别是首次发现了代表该类化合物C20原型骨架的系列新二萜，并以此为关键中间体，提出了该类二萜的生源合成途径。本项目拟在前期研究的基础上，对另外4种该属植物进行系统的化学和生物活性的研究，重点包括：1）发现具有抗肿瘤活性的新粗榧烷二萜；2）对不同植物以及同种植物不同部位中该类二萜的含量进行研究，以期发现富含粗榧烷二萜的植物和相关部位，为有效利用药用植物资源提供依据；3）对所获得的抗肿瘤化合物进行富集制备、结构优化和构效关系研究、以及进行深入的药理研究和作用机制探讨，以期发现抗肿瘤的药物先导，为研发新型抗肿瘤药物奠定基础。

Natural products are important resources for the discovery of antitumor drugs, and about 70% of the present clinical antitumor drugs are related with natural products. The Cephalotaxus genus are rich in resources and widely distributed in China. The cephalotane-type diterpenoids, which are rare in the Cephalotaxus species, were exhibited strong inhibitory effects on a panel of human tumor cell lines. Recently, our efforts resulted in the discovery of an array of antitumor cephalotane-type diterpenoids from Cephalotaxus species. The discovery of C20 cephalotane-type diterpenoids is particularly noteworthy, as this new skeleton could serve as the key biosynthetic intermediate for the coexistent antitumor analogues. On the basis of previous researches, this project will be conducted to study the chemical and biological activities of the other 4 Cephalotaxus species. The key points including the discovery of the new antitumor cephalotane-type diterpenoids, studies on the proportion of cephalotane-type diterpenoids in Cephalotaxus species to provide the basis for the effective utilization of medicinal plant resources, and modification and SAR study on biological active compounds to identify drug leads.