石蒜西啶类生物碱及衍生物抗烟草花叶病毒(TMV)的活性、构效关系和作用机制研究

从植物中发现具有抗植物病毒活性天然产物及衍生物是本课题组及申请者近几年重要的研究方向之一。前期研究从玉簪（Hosta plantaginea）、红花石蒜(Lycoris radiata)等植物中发现的石蒜西啶类生物碱成分具有很强的抗烟草花叶病毒（TMV）的活性，是本研究组发现的最强抗病毒活性成分之一。深入的研究提示该类化合物抗TMV病毒的活性有可能与其抑制植物寄主细胞中热休克蛋白Hsp 70的合成有关。本课题拟对石蒜西啶类生物碱及其衍生物通过TMV活性筛选，探讨该类生物碱及衍生物抗TMV的构效关系，并在此基础上，以活性显著的化合物作为小分子探针，探讨其作用机制和作用靶蛋白，以此帮助我们深入系统地认识石蒜西啶类生物碱抗TMV的途径，从而发现具有自主知识产权的抗TMV先导化合物，为我们今后从植物中寻找具有抗病毒天然先导化合物提供理论基础。

Approach on natural antivirus agents is a one important research field for our group. Earlier research have found in the different type of anti-TMV agents with different mechanisms from Strobilanthes cusia, Cynanchum paniculatum and some Simaroubaceae species, such as C-21 steroid,benzyl phenylethylamine alkaloids, quassioides, and carboline alkaloids.The results for further investigation indicated that pancratistatin-type alkaloids showed stronger anti-TMV activity, which perhaps related with their inhibition on the sytnesis of hsc 70 of host cell. This project focus investigation of structure-activity relationship, targeting protein and machanism of anti-TMV for pancratistatin-type alkaloids, in order to find the leads and clarify their effecting mechanism.