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

Nguyen, Michel; Li, Youzhi; Robert, Anne; Liu, Yan; Meunier, Bernard

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

detalle del documento

IDENTIFICACIÓN

oai:HAL:hal-04007798v1

Tema

Alzheimer's disease Catalytic oxidation Copper chelator Metabolism [CHIM]Chemical Sciences [CHIM.THER]Chemical Sciences/Medic...

Autor

Nguyen, Michel Li, Youzhi Robert, Anne Liu, Yan Meunier, Bernard

Langue

Editor

HAL CCSD;Wiley

Categoría

CNRS - Centre national de la recherche scientifique

Año

2023

fecha de cotización

29/9/2023

Palabras clave

alzheimer chelator disease tdmq20 copper

Métrico

Resumen

International audience; 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.

Nguyen, Michel,Li, Youzhi,Robert, Anne,Liu, Yan,Meunier, Bernard, 2023, Oxidation of TDMQ20, a Specific Copper Chelator as Potential Drug Against Alzheimer's Disease, HAL CCSD;Wiley