Journal
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
Volume -, Issue 10, Pages 1384-1388Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/ejic.201801332
Keywords
Alzheimer's disease; Copper; Chelates; Cu,Zn-superoxide dismutase; Cyanocobalamin; Biological activity
Categories
Funding
- NSFC [21502023]
- Guangdong Province (Program for Innovative Research Teams and Leading Talents Introduction) [2050205]
- GDUT [220418037]
- CNRS
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Copper chelators based on a tetradentate monoquinoline (TDMQ) scaffold are currently developed as potential drugs against Alzheimer's disease. Since TDMQ chelators have a high affinity for Cu-II and are expected to regulate copper homeostasis in the brain, the question whether these chelators might be able to demetalate, and therefore inhibit, essential copper proteins is obviously important, and should be answered before clinical development could be considered. We therefore examined the possible interaction of these chelators with physiological copper proteins, and related metal biomolecules. Our present work evidenced that TDMQ chelators (up to millimolar concentrations) do not affect in vitro the catalytic activities of Cu,Zn-superoxide dismutase and tyrosinase, two copper enzymes expressed in the brain and involved in the regulation of redox processes. In addition, TDMQ were found unable to demetalate vitamin B12, a Co-III cofactor essential for neurotransmitter synthesis and normal brain function. The validation of the compatibility between TDMQs and several physiological metal complexes is an important positive issue supporting the development of TDMQ chelators as drug-candidates.
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