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Issue 11, 2014
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Bimodal-hybrid heterocyclic amine targeting oxidative pathways and copper mis-regulation in Alzheimer's disease

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Abstract

Oxidative stress resulting from metal-ion misregulation plays a role in the development of Alzheimer's disease (AD). This process includes the production of tissue-damaging reactive oxygen species and amyloid aggregates. Herein we describe the synthesis, characterization and protective capacity of the small molecule, lipoic cyclen, which has been designed to target molecular features of AD. This construct utilizes the biologically compatible and naturally occurring lipoic acid as a foundation for engendering low cellular toxicity in multiple cell lines, radical scavenging capacity, tuning the metal affinity of the parent cyclen, and results in an unexpected affinity for amyloid without inducing aggregation. The hybrid construct thereby shows protection against cell death induced by amyloid aggregates and copper ions. These results provide evidence for the rational design methods used to produce this fused molecule as a potential strategy for the development of lead compounds for the treatment of neurodegenerative disorders.

Graphical abstract: Bimodal-hybrid heterocyclic amine targeting oxidative pathways and copper mis-regulation in Alzheimer's disease

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Publication details

The article was received on 10 Jun 2014, accepted on 13 Aug 2014 and first published on 21 Aug 2014


Article type: Paper
DOI: 10.1039/C4MT00161C
Citation: Metallomics, 2014,6, 2072-2082
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    Bimodal-hybrid heterocyclic amine targeting oxidative pathways and copper mis-regulation in Alzheimer's disease

    P. Gonzalez, V. C. P. da Costa, K. Hyde, Q. Wu, O. Annunziata, J. Rizo, G. Akkaraju and K. N. Green, Metallomics, 2014, 6, 2072
    DOI: 10.1039/C4MT00161C

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