中文摘要
基于川芎在抗脑缺血损伤方面显示出的优良药理活性和初步的化学研究基础,本项目拟采用药理活性跟踪筛选并结合不同的特异药物靶标,将现代微量、快速、在线等集成的分离分析策略与传统分离、分析技术相结合,从活性群中快速有效地识别、去重复、锁定与获取活性分子,尤其是微量新型活性成分,对常用中药川芎活性部位化学成分进行系统研究,并合成一系列苯酞(苷)类化合物,从影响脑缺血损伤三个途径,1)神经保护;2)抗血小板聚集作用;3)抗炎作用;对分离得到的化合物以及合成类似物进行活性评价和构效关系研究。重点探讨不同结构类型化合物对四种体外模型的作用规律,结合体内药效学实验,诠释川芎抗脑缺血损伤药效物质基础,同时力争获得川芎活性部位中抗脑缺血活性物质具有的基本结构特征,为创新药物研究提供先导结构,为进一步开发具有自主知识产权的新型药物奠定基础。
英文摘要
Based on the protective activity on cerebral ischemia injury of Ligusticum chuanxiong in vivo and in vitro, and the chemical consitituents isolated from Ligusticum chuanxiong. This project plans to study the chemical constituents of Ligusticum chuanxiong by using target isolation method combining with pharmacologcal results. Furthermore, a series of phthalide (glucosides) will be synthesized by the proposed route. On the basis of the above experiments, the project plans to choose neuron protection, antiplatelet aggregationand, and anti-inflammatory effect as the pharmaceutical screening target. The emphasis of this study is the effect of various structure type compounds on these three pharmacological targets. At the same time, the compounds with strong activity against cerebral ischemia injury will be selected, and then the animal model experiments will be applied. On the basis of these data, the bioactivity substances of would be clarified. Eventually, the bioactive compound would be a lead in drug discovery and a base of new medicine with self-owned intellectual property rights.
