具有抗肿瘤活性的糖基喹唑啉类分子的设计、合成及荧光性能的研究

针对现有抗肿瘤药物在细胞内毒性较大、药物寻靶不够精确且临床无法适时对该分子在活体肿瘤细胞内的作用及代谢过程进行追踪等问题，以抗胶质瘤药物分子的设计及合成为目标，依据分子设计及结构与药效关系等原理，对生物相容性好、寻靶精确且有荧光标识特征的糖基喹唑啉类化合物开展研究。首先，为解决糖环构型难以调控、官能团修饰复杂、分离提纯困难导致的糖基母核合成难度较大等难题，拟建立制备母核的脱羧偶联、碳氢活化等新合成方法；其次，开展其荧光成像功能、抗肿瘤活性等的研究，观察目标分子进入体内与肿瘤细胞发生相互作用的过程；探索细胞内的生物大分子、细胞内糖链与该分子糖链之间的相互作用，从而了解其在肿瘤中的生物学功能及干预调控作用机制。课题组在糖类化合物的生物相容性及兼具抗肿瘤活性、荧光标识作用的分子设计和合成研究方面有过创新性的尝试（见Chem. Sci. 2012,3:2388），并从中提炼出了本项目的科学问题。

This project is designed to solve the high toxicity of drug molecules towards cells, inaccurativity of the drug target, and not being able to be tracked in vivo tumor cells and metabolic process. On the basis of the structure-activity relationship theory, the research focuses on the design and synthesis of glycosyl quinazolines which have the fluorescent property, high targeting accuracy and good biocompatibility. Firstly, in order to solve the problems, such as lack of effective synthetic methods, difficultness of separation and analysis of carbohydrates, a new synthetic route including carboxyl coupling and C-H activation is developed. Secondly, this research is carried out on fluorescence imaging function, antitumor activity, and structure activity relationship. With the completion of this project, the process of these drugs into the body and tumor cell interaction can be visually monitored. Moreover, the molecular biological molecules and cells within the sugar chain, intracellular sugar chain and target molecule interaction between glycans are explored to better understand the mechanisms of biological function and the intervention effects on tumor. The design and synthesis of glycosyl heterocyclic compounds, study on biocompatibility, inhibition of tumor cells and in cells of the fluorescent has long been engaged in our group. We have done innovative attempt (Chem. Sci. 2012,3:2388) and extract the scientific points of the project.