他克林及其类似物抑制乙酰胆硷酯酶机理的理论研究  

THEORETICAL STUDIES ON THE MECHANISM OF INHIBITING AChE BY TACRINE AND ITS ANALOGUES

作　　者：李吉海[1] 高建军[1] 宋林青[1] 

机构地区：[1]山东大学化学院药物研究所,山东济南250100

出　　处：《山东大学学报（自然科学版）》2000年第2期207-211,共5页Journal of Shandong University(Natural Science Edition)

摘　　要：用MNDO半经验法 ,计算了乙酰胆碱酯酶 (AChE)抑制剂他克林及其类似物的优化构型、前线轨道、电荷分布 .并以这些量子化学参数讨论了它们抑制AChE的机制 .认为他克林嵌入AChE的苏丙氨酸 (F -3 3 0 )和色氨酸 (W -84 )之间 ,而形成一个“三明治”式夹心结构 .同时他克林喹啉环上的氮和组氨酸 -4 40的羰基形成氢键 ,使AChE活性中心的构象改变而使其活性降低或失活 .The geometries,frontier orbits and charges distribu ti on of Tacrine and its analogies were calculated by semi empirical scheme MNDO.T he mechanism of inhibiting AChE was emphatically discussed with this quantum dat e.It was considered that the Tacrine or its analogies are embedded between F 30 0 and W 84 of AChE.The Tacrine is thus sandwiched between F 300 and W 84 to o btain the best interaction,meanwhile the hydrogen bond is formed between atom N in quinoline ring of Tacrine and carboxide of histidine 400.As result the conf ormation of active site is changed to made the activity of AChE decrease or lose wholly.

关 键 词：他克林 乙酰胆碱酯酶 早老性痴呆 抑制剂 药物 

分 类 号：R971.92[医药卫生—药品] R749.160.5[医药卫生—药学]