Laboratoire de Chimie de Coordination du Centre National de la Recherche Scientifique (CNRS) 205 route de Narbonne, BP 44099, 31077 Toulouse cedex 4 (France).
Laboratoire de Chimie de Coordination du Centre National de la Recherche Scientifique (CNRS) 205 route de Narbonne, BP 44099, 31077 Toulouse cedex 4 (France) ; Department of Chemical Engineering, Guangdong University of Technology, Education Mega Center 100 Waihuan Xi Rd, Guangzhou (P. R. China).
ChemistryOpen. 2015 Feb;4(1):27-31. doi: 10.1002/open.201402075. Epub 2014 Oct 27.
The accumulation of redox-active metal ions, in particular copper, in amyloid plaques is considered to the cause of the intensive oxidation damage to the brain of patients with Alzheimers disease (AD). Drug candidates based on a bis(8-aminoquinoline) tetradentate ligand are able to efficiently extract Cu(2+) from copper-loaded amyloids (Cu-Aβ). Contrarily, in the presence of a bidentate hydroxyquinoline, such as clioquinol, the copper is not released from Aβ, but remains sequestrated within a Aβ-Cu-clioquinol ternary complex that has been characterized by mass spectrometry. Facile extraction of copper(II) at a low amyloid/ligand ratio is essential for the re-introduction of copper in regular metal circulation in the brain. As, upon reduction, the Cu(+) is easily released from the bis(8-aminoquinoline) ligand unable to accommodate Cu(I), it should be taken by proteins with an affinity for copper. So, the tetradentate bis(8-aminoquinoline) described here might act as a regulator of copper homeostasis.
氧化还原活性金属离子（尤其是铜）在淀粉样斑块中的积累被认为是阿尔茨海默病（AD）患者大脑受到强烈氧化损伤的原因。基于双（8-氨基喹啉）四齿配体的药物候选物能够从负载铜的淀粉样蛋白（Cu-Aβ）中有效提取 Cu（2+）。相反，在存在双齿羟基喹啉（如氯碘羟喹）的情况下，铜不会从 Aβ 中释放出来，而是被螯合在 Aβ-Cu-氯碘羟喹三元复合物中，该复合物已通过质谱进行了表征。在低淀粉样蛋白/配体比下，铜（II）的易提取对于将铜重新引入大脑中正常的金属循环至关重要。因为，当还原时，Cu（+）很容易从不能容纳 Cu（I）的双（8-氨基喹啉）配体中释放出来，因此应该被具有铜亲和力的蛋白质带走。因此，这里描述的四齿配体双（8-氨基喹啉）可能作为铜动态平衡的调节剂。
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