以活性天然产物为苗头，展开天然产物杂合物的合成与活性研究，从而发现更具成药性的活性先导物，是新药创制的重要途径。C23萜类化合物是由鼠尾草属植物中发现的一类结构独特、活性显著的微量天然产物。前期研究中我们发现Danshenol A和Przewalskone这两个结构新颖的Danshenol型C23萜类化合物对多种人肿瘤细胞株具有显著的体外生长抑制活性，且呈现较好的选择性；其作用与NF-κB这一抗肿瘤重要信号通道密切相关。本项目拟在此基础上，以鼠尾草属植物中丰富的二萜化合物为原料，通过合成化学的手段，构建结构与DanshenolA和Przewalskone密切相关的天然产物杂合物库，并对库中化合物并行进系统的抗肿瘤活性研究；探讨该类化合物抗肿瘤活性的构效关系与作用机制；以期发现更具成药性的先导化合物。为鼠尾草属植物二萜化合物的有效利用提供新思路，为创新药物研究提供新药候选。

It's an important way to search lead compounds from the library of natural products hybrids constructed on the basis of bioactive metabolites. Danshenol A and przewalskone, two C23 terpenoid analogues isolated from Salvia plants, were found to exhibit significant toxicities to the tested human cancer cell lines while non-toxicity toward the normal human bronchial epithelial cell line (Beas-2B) in our study. Based on these findings, we plan to construct a library of the natural products hybrids structurally related to Danshenol A and przewalskone from the major diterpenoids from Salvia plants. And then, a systematic bioactive studies including the mechanism and SAR of these natural products hybrids will be carried out to search for new bioactive compounds with more druggability. The result should benefit for the comprehensive usage of abundant terpenoid constituents of Salvia plants, and provide new candidate for the development of new drugs.