鼠李科美洲茶烷型三萜抗肿瘤活性及其构效关系研究

Cancer has high incidence and mortality, which do great harm to people's life. To search efficient natural lead compound with low toxicity is one of the important direction in antitumor drug development. Ceanothane type triterpenoid is a kind of rarely found pentacyclic triterpene, the representative compound, ceanothic acid, which has a similar skeleton with lupane type triterpene, but has the only difference in the contracted five-membered Ring-A. This kind compounds mainly exist in Rhamnaceae family plants (such as the genus of Ziziphus, Paliurus, Hovenia, etc.), and their antitumor, antibacterial and antimalarial activities, which only reported in a few amount of literature. Previously, we obtained many of this type compounds, including a series of novel skeleton, from roots of Z. mauritiana. Partial compounds showed their cytotoxity and antibacterial activity significantly, and the results exhibited a structure-activity relationship (SAR) to some extent. In order systematically and deeply to research the antitumor activity and SAR of these substances, this project will carry out the directional isolation of novel ceanothane triterpenes from the twigs and leaves of Z. mauritiana, and from P. ramosissimus, P. hemsleyanus and H. acerba grown in Jiangxi Province, on the basis of preliminary results. On the other hand, we will perform the structure transformation or modification by introducing active group to get many more candidate compounds, and search stronger active molecules by antitumor activity screening assay, to complete the SAR research of ceanothane triterpenoids. The implementation of project will promote the study of ceanothane type triterpenoids, and lay a scientific foundation for finding efficient anticancer drug candidates or lead compounds.

癌症具有高发、高死亡率，对生命危害巨大，寻找高效低毒的天然抗肿瘤活性先导化合物是目前药物研发的重要方向之一。美洲茶烷型三萜是一类发现较少的五环三萜，其与羽扇豆烷型三萜结构相似，差异仅在于其A环为五员缩环结构，代表性成分为美洲茶酸。该类成分主要存在于鼠李科植物（如枣属、马甲子属、枳椇属等）中，仅有少量抗肿瘤、抗菌、抗疟等活性文献报道。前期我们从枣属植物中分离得到多种该类三萜，包括一系列新颖结构，通过肿瘤细胞毒活性和抗菌活性筛选，发现部分化合物具有显著的活性，初步显示出一定的构效关系。本项目拟在已有研究基础上，从滇刺枣及江西产马甲子、铜钱树、枳椇等植物枝叶中定向发掘新的美洲茶烷类三萜成分，并通过结构修饰引入活性基团，进行抗肿瘤活性筛选，寻找更强活性分子，系统研究和完善其构效关系。项目实施将会促进该类化学成分研究，为发现高效抗肿瘤候选药物或先导化合物奠定科学基础。