期刊
CHEMISTRYOPEN
卷 4, 期 1, 页码 27-31出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/open.201402075
关键词
Alzheimers disease; chelating agents; copper homeostasis; medicinal chemistry; therapeutic agents
资金
- French National Centre for Scientific Research (CNRS)
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 Cu2+ from copper-loaded amyloids (Cu-A beta). Contrarily, in the presence of a bidentate hydroxyquinoline, such as clioquinol, the copper is not released from A beta, but remains sequestrated within a A beta-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.
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