Journal
CHEMMEDCHEM
Volume 13, Issue 7, Pages 684-704Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.201700734
Keywords
Alzheimer's disease; copper ligands; metal homeostasis; reactive oxygen species
Categories
Funding
- National Natural Science Foundation of China [21502023]
- Government of Guangdong Province [2050205]
- Guangdong University of Technology [220418037]
- Institut National de Chimie, Centre National de la Recherche Scientifique
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The uncontrolled redox activity of metal ions, especially copper, in the brains of patients with Alzheimer's disease (AD) should be considered the origin of intense oxidative damage to neurons in the AD brain. To obtain low-molecular-weight copper chelators that act as tetradentate ligands, we designed new compounds based on an 8-aminoquinoline motif with a lateral chain attached at the 2-position of the aromatic ring. Some of these new ligands, termed TDMQ for TetraDentate MonoQuinolines, are specific for copper chelation. Full characterization of these ligands is reported, as well as their affinities for Cu-II, and their capacities to inhibit oxidative stress induced by copper-amyloids activated by a reductant. Such metal ligands can be considered as potential anti-AD agents, as they should be able to regulate the homeostasis of copper in brain tissue.
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