蜡梅属植物中乙酰胆碱酯酶抑制剂先导化合物的发现及构效关系研究

项目名称： 蜡梅属植物中乙酰胆碱酯酶抑制剂先导化合物的发现及构效关系研究

项目编号： No.31260082

项目类型： 地区科学基金项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 邹峥嵘

作者单位： 江西师范大学

项目金额： 47万元

中文摘要： 阿尔茨海默病(AD)是一种原发性中枢神经系统退行性疾病，抗乙酰胆碱酯酶药物是AD靶向治疗的重要手段，是阿尔茨海默病新药研发的热点方向。申请者在对突托蜡梅化学成分进行系统分离纯化研究的过程中，发现其乙醇提取物及分离馏分显示较强的抗乙酰胆碱酯酶活性。本课题拟在此基础上，以薄层层析-生物自显影联用等活性检测方法为指导，采用多种分离纯化技术和GC-MS、LC-MS、HPLC-NMR联用等技术从突托蜡梅、山蜡梅和柳叶蜡梅等三种蜡梅属中定向追踪分离具抗乙酰胆碱酯酶活性的化合物；根据化合物的理化性质、波谱特征和HPLC手性表征等确定其化学结构；采用化学衍生化结构改造和体内活性检测方法探讨活性化合物抗乙酰胆碱酯酶的作用机制及构效关系，寻找结构新颖的抗乙酰胆碱酯酶化合物，为研制作用机制明确、副作用小的抗乙酰胆碱酯酶药物提供先导化合物，同时也为蜡梅属植物的科学分类提供化学分类学依据。

中文关键词： 蜡梅属；乙酰胆碱酯酶；抑制剂；先导化合物；构效关系

英文摘要： Alzheimer's disase (AD) is a chronic neurodegenerative disorder that results in the progressive and irreversible loss of higher brain functions, such as impaired memory, thinking and behaviour in the elderly. One of the well-established theory on the causes of AD suggests that the neurotransmitter acetylcholine levels are too low in the brains of AD patients. Current treatment approaches for this disease remain primarily symptomatic with major therapeutic strategy being based on the cholinergic hypothesis and specifically on the cholinergic inhibition. The first approved drug for the managentment of AD was tacrine. Although several acetylcholinesterase inhibitor have been developed, they are only useful for treating patients with mild to moderate AD. The development of more effective anti-AD agents is still an important area of AD-associated research. Chimonanthus is a genus endermic to China.In the before research, we have found the cholinergic inhibition activity of the fractions isolated from Chimonanthus grammatus.So,we dicided to isolate and purify the constituents that have the ACh E inhibition activity from 3 species of the genus chimonanthus by means of column chromatography such as Si Gel,ODS, Shaphadex LH-20 guided by TLC-bioautography, the stuctures of the constituents will be elucidated on the

英文关键词： chimonanthus；acetylcholinesterase；inhibitor；leading compounds；structure-activity relationship