Aroylhydrazones constitute a promising class of 'metal-protein attenuating compounds' for the treatment of Alzheimer's disease: a proof-of-concept based on the study of the interactions between zinc(II) and pyridine-2-carboxaldehyde isonicotinoyl hydrazone

Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry
D S CukiermanN A Rey

Abstract

With the increasing life expectancy of the world's population, neurodegenerative diseases, such as Alzheimer's disease (AD), will become a much more relevant public health issue. This fact, coupled with the lack of efficacy of the available treatments, has been driving research directed to the development of new drugs for this pathology. Metal-protein attenuating compounds (MPACs) constitute a promising class of agents with potential application on the treatment of neurodegenerative diseases, such as AD. Currently, most MPACs are based on 8-hydroxyquinoline. Recently, our research group has described the hybrid aroylhydrazone containing the 8-hydroxyquinoline group INHHQ as a promising MPAC. By studying the known structure-related ligand HPCIH, which does not contain the phenol moiety, as a simplified chemical model for INHHQ, we aimed to clarify the real impact of the aroylhydrazone group for the MPAC activity of a compound with potential anti-Alzheimer's activity. The present work describes a detailed solution and solid-state study of the coordination of HPCIH with Zn2+ ions, as well as its in vitro binding-ability towards this metal in the presence of the Aβ(1-40) peptide. Similar to INHHQ, HPCIH is able to efficiently compe...Continue Reading

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Citations

Apr 25, 2019·International Journal of Molecular Sciences·Thais A SalesTeodorico C Ramalho
Aug 11, 2020·Expert Opinion on Emerging Drugs·Madia LozuponeFrancesco Panza
Aug 12, 2019·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Daphne S CukiermanNicolás A Rey
Jun 23, 2020·Journal of Alzheimer's Disease : JAD·Johant Lakey-BeitiaK S Rao
Feb 8, 2021·European Journal of Medicinal Chemistry·Cauê Benito ScarimFernando Rogério Pavan
Sep 7, 2021·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Nevena StevanovićKatarina Anđelković

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Methods Mentioned

BETA
X-ray
isothermal titration calorimetry
NMR
Nuclear magnetic resonance

Software Mentioned

Osiris Property Explorer : [UNK]
Fit
SAINT
Topspin
OLEX2
CCPN
Wingx
SHELXL
SHELXS

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