Alzheimer's Disease (AD), reported for the first time in 1906, is a common disease that remains incurable to this day. In the past, a family of treatments using Cu(II) chelators failed during clinical trials, evidencing the importance of pre-clinical studies. In this work, we performed electrochemical characterisation of TDMQ20, a new potential drug against AD, using electrochemistry and spectroelectrochemistry. On the basis of voltammetry, we determined that TDMQ20 undergoes a two-step irreversible oxidation process and a one-step irreversible reduction process. Both oxidation and reduction reactions are pH-sensitive. Bidimensional UV-Vis spectroelectrochemistry (UV-Vis-SEC) allowed us to confirm that oxidation of TDMQ20 can occur both on the aliphatic chain and on the aromatic ring. The results expand the knowledge of the TDMQ20 redox activity in the human body which is important from the point of view of the toxicity of the proposed therapy.

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http://dx.doi.org/10.1016/j.bioelechem.2024.108814DOI Listing

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Alzheimer's Disease (AD), reported for the first time in 1906, is a common disease that remains incurable to this day. In the past, a family of treatments using Cu(II) chelators failed during clinical trials, evidencing the importance of pre-clinical studies. In this work, we performed electrochemical characterisation of TDMQ20, a new potential drug against AD, using electrochemistry and spectroelectrochemistry.

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TDMQ20, a Specific Copper Chelator, Reduces Memory Impairments in Alzheimer's Disease Mouse Models.

ACS Chem Neurosci

January 2021

School of Chemical Engineering and Light Industry, Guangdong University of Technology (GDUT), Higher Education Mega Center, 100 Waihuan Xi Road, Panyu District, Guangzhou 510006, P. R. China.

Besides targeting amyloid or tau metabolisms, regulation of redox metal ions is a recognized therapeutic target for Alzheimer's disease (AD). Based on the bioinorganic chemistry of copper, we designed specific chelators of copper(II) (TDMQs) insight to regulate copper homeostasis in the brain and to inhibit the deleterious oxidative stress catalyzed by copper-amyloid complexes. An oral treatment by TDMQ20 was able to fully reverse the cognitive and behavioral impairment in three different murine models, two nontransgenic models mimicking the early stage of AD and a transgenic model representing a more advanced stage of AD.

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