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OALib Journal期刊
ISSN: 2333-9721
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双烟碱衍生物作为胆碱酯酶和β-淀粉样蛋白双功能抑制剂的设计、合成及活性
, PP. 1671-1676
Keywords: 烟碱衍生物,胆碱酯酶,β-淀粉样蛋白,抑制剂,阿尔茨海默症
Abstract:
本文设计合成了一系列双烟碱衍生物(3a～3i)作为双功能的抗阿尔茨海默症药物。活性测试结果表明这类衍生物对乙酰胆碱酯酶(acetylcholinesterase,ache)和丁酰胆碱酯酶(butyrylcholinesterase,bche)的抑制活性达到微摩尔级,其中化合物3f活性最强,对ache和bche的ic50值分别为2.28和1.67μmol·l-1,优于对照药物rivastigmine。酶动力学及分子对接表明3f能够同时作用于ache的催化活性位点(catalyticactivesite,cas)和外周结合位点(peripheralanionicsite,pas)。而且这类衍生物在20μmol·l-1浓度下能够明显抑制β-淀粉样蛋白(β-amyloid,aβ)的自聚集。
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