山豆根中具有抗肿瘤活性的Cytisine-Pterocarpan型新骨架化合物的发现及其仿生合成研究

项目名称： 山豆根中具有抗肿瘤活性的Cytisine-Pterocarpan型新骨架化合物的发现及其仿生合成研究

项目编号： No.81502941

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 李行诺

作者单位： 浙江工业大学

项目金额： 17.9万元

中文摘要： Cytisine与Pterocarpan型化合物均具有良好而广泛的生物活性，一直是药物化学研究的热点。通过前期工作，我们从山豆根中获得了两个具有Cytisine-Pterocarpan偶联的新骨架化合物，并对其抗肿瘤活性进行了初步筛选。本项目拟利用高含量成分逐级过滤技术，结合多种LC/MSn、MPLC、Semi-Pre HPLC等技术，从山豆根中快速、准确的发现和获取具有Cytisine-Pterocarpan骨架的新化合物，并对该新骨架进行仿生合成研究，同时对该类型化合物的抗肿瘤活性、选择性和作用机制进行研究。通过本研究，从山豆根中获得结构多样的具有该骨架的化合物，构建该新骨架的仿生合成路线，并初步阐明其抗肿瘤机理。该研究不仅为具有抗肿瘤活性的Cytisine-Pterocarpan新骨架化合物的发现及合成奠定了基础，同时也为低含量天然产物的识别与获取提供新的研究思路。

中文关键词： 山豆根；新骨架化合物；抗肿瘤；仿生合成；作用机制

英文摘要： Due to the good and extensive bioactivities, the researches on the compounds of cytisine and pterocarpan have become the hot topics in medicinal chemistry. According to our previous research, Tonkinensines A and B, two novel cytisine-type alkaloids that feature the skeleton with a linkage to pterocarpan, were isolated from the roots of Sophora tonkinensis. Both of them were tested in HeLa and MDA-MB-231 tumor cell lines, and Tonkinensines B showed moderate cytotoxic activity. On the basis of modern techniques such as LC/MSn, MPLC, and Semi-Pre HPLC, the High Components Filtering Strategy will be employed to track and obtain many more target compounds with the Cytisine-Pterocarpan skeleton rapidly and accurately. And the biomimetic synthesis of the new skeleton will be undertaken using the organic synthesis. MDA-MB-231 and MCF-10A cells will be used to evaluate the antitumor bioactivity and selectivity of these compounds in vitro. And the mechanism of the cell apoptosis will be referred in the research. According to this project, many more Cytisine-Pterocarpan compounds with the structural diversity will be obtained. And a synthetic route will be fit for the biomimetic synthesis. The summary of the structure-activity relationship and the mechanism will be clear base on the results of antitumor activities. The researches of the project were expected not only to construct the foundation for the discovery and synthesis of the antitumor constituents with the novel Cytisine-Pterocarpan skeleton, but also to provide a new method for tracking and obtaining low content compositions in natural medicines.

英文关键词： Sophora tonkinensis;compounds with novel skeleton;antitumor;biomimetic synthesis;mechanism