Dokumentdetails
ID
oai:HAL:hal-04007798v1
Thema
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, BernardLangue
enEditor
HAL CCSD;Wiley
Kategorie
CNRS - Centre national de la recherche scientifique
Jahr
2023
Auflistungsdatum
29.09.2023
Schlüsselwörter
alzheimer chelator disease tdmq20 copperZusammenfassung
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
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