Journal
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
Volume -, Issue 25, Pages 3198-3204Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/ejic.201700385
Keywords
Alzheimer's disease; O ligands; Copper; Iron; Ligand design
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Funding
- Centre National de la Recherche Scientifique (CNRS)
- Guangdong University of Technology (GDUT)
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The loss of homeostasis of redox metal ions, namely, copper and iron, has been considered to be an important contributing factor in neuronal death observed in the brain of patients affected by Alzheimer's disease (AD). Specific ligands able to regulate the homeostasis of copper and, to a lesser extent, iron ions in the brain have therefore been considered to be potential drugs for the treatment of AD. Herein, the synthesis and metal coordination properties of a series of ligands based on a bis(2,3-dihydroxyalkylbenzamide) scaffold, which are po-tentially able to regulate the homeostasis of redox metal ions, are reported. These catechol-based ligands exhibit high specific affinities for Cu-II and Fe-III, and a lower affinity for Zn-II, which indicates that they may interact with redox metal ions without disturbing the structural and dynamic role of zinc chelation in many proteins. These ligands inhibit the reduction of dioxygen induced by Cu-II-A beta(1- 16), and this suggests that they may be able to efficiently reduce the oxidative stress induced by metal-loaded amyloids in the AD brain.
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