基于PTP1B靶点的新型T2DM抑制剂—江西两种刺桐属植物中特异性异戊烯基化紫檀烷类成分及构效关系和作用机制研究

蛋白酪氨酸磷酸酶1B(PTP1B)在胰岛素信号调节中起重要的负调节作用，组织细胞中PTP1B过表达会降低蛋白酪氨酸激酶的活性，使胰岛素受体无法与胰岛素结合，进而发生糖脂代谢紊乱，最终导致2型糖尿病(T2DM)。因此，寻找和发现高效、低毒、高选择性的PTP1B抑制剂作为抗T2DM药物具有重要意义。. 本项目在已从鸡冠刺桐中分离鉴定出11种刺桐属植物特征性、具明显选择性抑制PTP1B的异戊烯基化紫檀烷类新颖结构化合物的基础上，拟对江西两种刺桐属植物龙牙花和翅果刺桐中的异戊烯基化紫檀烷类成分进行定向分离和结构鉴定，并对该类化合物进行体外PTP1B抑制活性、体内降糖作用、构效关系和作用机制研究，以期获得一些可明显抑制PTP1B的新型抗T2DM药物先导化合物。本课题的开展将为开发利用我国刺桐属药用植物资源积累一定的资料，为PTP1B抑制类抗T2DM药物的研究与开发提供一定的科学依据。

Protein tyrosine phosphatase 1B (PTP1B) is an important negative regulator of insulin signal transduction in vivo. In various tissue cells, overexpression of PTP1B results in a decrease in the activity of protein tyrosine kinase, which blocks interactions of insulin receptor with insulin and further lead the individual to insulin resistance. Finally, the metabolism of glucose and lipid is also disturbed, resulting in the pathogenesis of type 2 diabetes mellitus (T2DM). Therefore, it is of great significance to discover new anti-T2DM drug targeting PTP1B with high efficiency, low toxicity, and high selectivity.. 11 Novel prenylated pterocarpans characteristic of the plants of the genus Erythrina, which exhibited selective and potent PTP1B inhibitory activity, have been isolated from Erythrina crista-galli in our previous experiments. This project will deal with the discovery of natural product-based on PTP1B inhibitors from two plants of the genus Erythrina (E. corallodendron and E. subumbrans) distributed in Jiangxi on the basis of these findings. The aim of this research is to search for characteristic prenylated pterocarpans from the Erythrina genus, to evaluate for PTP1B inhibitory activity, hypoglycemic effect in vivo, structure-activity relationship, and mechanism of action of this type of compounds, and to obtain several lead compounds for new anti-T2DM drugs targeting PTP1B. This research will be to afford more theoretic and experimental data for investigation of rich source of the Chinese Erythrina plants ande to provide certain scientific data for the discovery of new anti-T2DM drugs targeting PTP1B.