活性官能团导向的抗肿瘤全新化学实体的结构优化及作用机制研究

项目名称： 活性官能团导向的抗肿瘤全新化学实体的结构优化及作用机制研究

项目编号： No.21272107

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 林利

作者单位： 兰州大学

项目金额： 80万元

中文摘要： 肿瘤已成为人类生命健康的主要杀手，抗肿瘤新药创制作为化疗的重要手段日益受到人们的关注。本项目涉及一类活性官能团导向的抗肿瘤全新化学实体，通过源头方法创新获得，属1.1类化学新药先导化合物。项目以前期抗肿瘤药效学研究为基础，拟针对提高先导化合物的抗肿瘤活性、水溶性对其进行成药性结构优化，通过对其引起细胞凋亡的具体途径研究、CAAD辅助药物-酶蛋白对接实验、DNA复制及端粒酶活性的相关调控研究，以期阐明此类化合物的具体作用机制，明确作用靶点，结合初步安全评价为其成药性评价提供可靠的理论和实验支持。本项目具有良好的工作基础，研究方案切实可行；此类药物构效关系新颖独特，其抗肿瘤活性及作用机制研究未见报道，创新性强；技术路线体现了多学科实验手段在新药研发中的有机结合，具有较强的创新性。项目开展对探索抗肿瘤的新途径、新作用机制具有重要的理论指导意义，对抗肿瘤新药创制具有重要应用价值。

中文关键词： 新药发现；构效关系；合成方法学；不对称催化；抗肿瘤机制

英文摘要： Cancer has become the main murderer of humanity life and health. As one of the most important means of chemotherapy, anti-tumor drug discovery has received people's increasing attention. This project involves a class of active functional group oriented novel anti-tumor chemical compound. This No. 1.1 class of new chemical drug lead can be obtained through innovative synthetic approaches. This project is based on our initial pharmacodynamics investigations. Further pharmacophore studies would be developed intending to improve the anti-tumor activity as well as water-solubility. The specific medicinal mechanism would be revealed via the apoptotic pathway study, CAAD assistance medicine-protein docking experiment, the DNA duplication regulation study, as well as telomerase activity related regulation. In combination with the preliminary safety evaluation, these studies could provide reliable theoretical and experimental supports for the pharmacodynamical evaluation. The project is based on good and solid foundations. The study protocol has been well analyzed, and reasonable, practicable, as well as feasible. The structure-activity relationship of the related leads is novel and distinctive. The anti-tumor activity and the mechanism study of this type of compound have not been reported before, and with strong innovat

英文关键词： new drug discovery；structure-activity relationship；synthetic methodology；asymmetric catalysis；anti-tumor mechanism