摘要/Abstract

阿尔茨海默（AD）脑内氧化还原活性金属离子稳态失衡，尤其是铜离子的稳态失衡，是引起氧化应激，从而导致AD脑内氧化损伤的重要原因.为了开发选择性的铜离子螯合剂，以开发抑制AD氧化应激先导化合物，以2-甲基-8-硝基喹啉为原料，经过硝基还原、C2位氧化（官能团化）、还原胺化、加成等反应合成了具有四配位螯合作用的喹啉衍生物.通过调节侧链的长度及配位原子的位置，对化合物的络合能力、对Cu（Ⅱ）和Zn（Ⅱ）的选择性进行了研究.其中，TDMQ29对铜离子有特异选择性，log K_app[Cu^Ⅱ-TDMQ29]为15.7，而log K_app[Zn^Ⅱ-TDMQ29]为5.8，对铜离子的络合常数比对锌离子的络合常数高出10个数量级.
关键词: 阿尔茨海默症, 8-氨基喹啉, 铜离子螯合, 选择性
The non-controlled redox-active metal ions, especially copper, in the brain of patients with Alzheimer disease (AD) should be considered at the origin of the intense oxidative damage in AD brain. In this paper, we designed and synthesized new compounds based on 8-aminoquinoline motif with a lateral chain at the C2 position of the aromatic ring. The affinities for Cu(Ⅱ) and Zn(Ⅱ) of these ligands are reported in the present article. Among these chelators, TDMQ29 is specific for copper chelation with log K_app[Cu^Ⅱ-TDMQ29] to be 15.7 and log K_app[Zn^Ⅱ-TDMQ29] to be 5.8. Such metal ligands can be consi-dered as potential ligands, which are able to regulate the homeostasis of copper in brains.
Key words: Alzheimer disease (AD), 8-aminoquinoline, copper chelation, selectivity


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