Aroylhydrazones constitute a promising class of ‘metal-protein attenuating compounds’ for the treatment of Alzheimer’s disease: a proof-of-concept based on the ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-12

AUTHORS

Daphne S. Cukierman, Elio Accardo, Rosana Garrido Gomes, Anna De Falco, Marco C. Miotto, Maria Clara Ramalho Freitas, Mauricio Lanznaster, Claudio O. Fernández, Nicolás 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 compete with Aβ(1-40) for Zn2+ ions, performing as expected for an MPAC. The similarity between the behaviors of both ligands is remarkable. Taken together, the data presented herein point to aroylhydrazones, such as the compounds HPCIH and the previously published INHHQ, as encouraging MPACs for the treatment of AD. More... »

PAGES

1-15

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00775-018-1606-0

DOI

http://dx.doi.org/10.1007/s00775-018-1606-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1106340469

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30145655


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s00775-018-1606-0'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s00775-018-1606-0'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s00775-018-1606-0'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s00775-018-1606-0'


 

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