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Article Dans Une Revue ChemistrySelect Année : 2023

Oxidation of TDMQ20, a Specific Copper Chelator as Potential Drug Against Alzheimer's Disease

Résumé

Developed as a regulator of copper homeostasis in the brain of patients affected by Alzheimer's disease (AD), TDMQ20 is a specific copper(II) chelator able to restore short term memory in AD mice. To anticipate on metabolic studies of this drug-candidate, here we report the catalytic oxidation of TDMQ20 by a biomimetic system reminiscent of P450 oxidation, using a metalloporphyrin and hydrogen persulfate as oxidant. Oxidation products were mainly characterized by HPLC with UV-visible spectrometry or high-resolution mass spectrometry detection. In these conditions, TDMQ20 was readily oxidized by aromatic hydroxylation, oxidation of 1,4-diphenol or 1,4-aminophenol to 1,4-quinone or quinone-imine, respectively, or oxidative chlorination. These putative metabolites were water-soluble, suggesting that the drug-candidate might be easily metabolized and excreted in vivo.
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Dates et versions

hal-04007798 , version 1 (28-02-2023)

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Michel Nguyen, Youzhi Li, Anne Robert, Yan Liu, Bernard Meunier. Oxidation of TDMQ20, a Specific Copper Chelator as Potential Drug Against Alzheimer's Disease. ChemistrySelect, 2023, 8 (8), pp.e202204877. ⟨10.1002/slct.202204877⟩. ⟨hal-04007798⟩
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