基于苦参碱结构的新骨架衍生物的合成、抗肿瘤构效关系和作用机理研究

项目名称： 基于苦参碱结构的新骨架衍生物的合成、抗肿瘤构效关系和作用机理研究

项目编号： No.21262005

项目类型： 地区科学基金项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 王立升

作者单位： 广西大学

项目金额： 54万元

中文摘要： 癌症已成为全球性的问题，死亡率高，治疗难度大，严重地威胁着人类的生命健康。因此，寻找和开发新型抗癌药物势在必行。本项目在已有对苦参碱研究工作的基础上，设计合成一系列新骨架结构的衍生物。探索合成方法，优化合成参数，并采用波谱分析手段表征目标化合物的结构。采用艾氏腹水癌等药理实验模型进行体内抗肿瘤药理活性测定，结合计算机辅助手段，研究目标化合物的构效关系。在细胞和分子水平上，研究目标化合物对肿瘤细胞的增值抑制、粘附与浸润转移抑制、诱导凋亡等作用，并进一步研究苦参碱衍生物对肿瘤相关基因的调控机制，明确目标化合物的作用机理。对目标化合物进行分子对接研究，从与靶标蛋白的结合方式上，明确化合物活性与靶标相互作用的关系。研究结果将为进一步设计有效地抗肿瘤药物候选物，开发新药建立基础。

中文关键词： 苦参碱衍生物；合成；抗肿瘤活性；作用机理；分子对接

英文摘要： Cancer has become a global issue with its high mortality and great remedial difficulty, and been threatening human health and life. Thus, it is imperative to seek and develop novel anticancer drugs. Based on the previous research of matrin in our group, we will design and synthesize a series of matrine derivatives with novel skeleton structures in the project. Necessarily, we will also study the synthesis methods and optimize relative parameters, and use spectroscopy analysis to characterize the structures of target compounds. In vivo antitumor activities of target compounds will be evaluated by pharmacological experimental models such as Ehrlich's ascites carcinoma and so on. The structure-activity relationships will be analyzed by computer aided methods. Inhibition effects of target compounds on proliferation, adhesion, infiltration and metastasis of tumor cells and induced apoptosis of tumor sells will be researched in cellular and molecular levels. The regulation mechanism of tumor-relative genes for matrine derivatives will be further studied. Finally, the effect mechanism of the compounds will be clarified. From the combination pattern of the targeted protein and the compounds in molecular docking, we will get the interaction relationships between anti-tumor compounds and the drug target. The research resu

英文关键词： Matrine derivative；Synthesis；Anti-tumor activity；Effective mechanism；Molecular docking