基于天然环烯醚萜的拟单萜吲哚生物碱类似物的制备及其抗肿瘤活性研究

从天然产物中寻找新候选药物分子仍是发展创新天然药物的有效途径之一，但从植物中直接获得化合物的过程相对繁琐且历时长，得到的化合物结构差异通常相对较小，从而制约了其进一步生物学研究。如以某一类天然成分作为合成砌块，依据所需天然产物生源途径，利用仿生合成方法得到若干结构与天然产物相似但又异于天然产物的“拟天然产物”，进而对其进行系统活性筛选，即能发现新先导物，又能极大丰富天然产物类似物库。基于上述组合化学和仿生合成的思路，项目组前期以含天然环烯醚萜单元的栀子苷元作为合成模块，与色胺及其衍生物通过仿生合成途径制备并发现了若干抗肿瘤活性显著的新拟单萜吲哚生物碱类似物，但结构缺乏多样性，本项目拟在此基础上选取3类天然环烯醚萜苷元分别与色胺及其衍生物通过仿生合成制备系列拟单萜吲哚生物碱类似物，并评价其抗肿瘤活性，以期发现抗肿瘤活性更强的化合物，为发现结构新颖、机制独特的抗肿瘤候选药物分子提供物质基础。

Finding new candidate drug molecules from natural products is still one of an effective way to develop innovative natural medicines at present. However, the process of obtaining compounds from plants is relatively tedious and long-lasting, and the structural differences of the obtained compounds are relatively small, thus restricting their further Biological research. If a certain kind of natural ingredients can be used as a building block, some " natural products-like" which have similar structures to those of natural products but different from natural products can be obtained by biomimetic synthesis according to the synthetic pathway of natural products, and then their biological activity is screened. It is highly probable that a new leader will be found which will greatly enrich the compound library of natural product analogs. Based on the above ideas of biomimetic synthesis and combinatorial chemistry, the project team used geniposidone with iridoid units as a synthesis module and prepared and found several new antitumor products with tryptamine and its derivatives through biomimetic synthesis. Active pseudomonoterpene indole alkaloid analogues. Therefore, this project intends to select three types of natural iridoid and tryptamine and their derivatives through the bionic synthesis respectively to prepare a series of pseudo-monoterpene indole alkaloids. The antitumor activity will be studied in order to find compounds with better anti-tumor activity, which provided the material basis for the discovery of novel anticancer drug molecules with structure and mechanism.