Disruption of zinc and copper interactions with Aβ(1-40) by a non-toxic, isoniazid-derived, hydrazone: a novel biometal homeostasis restoring agent in Alzheimer's disease therapy?

R A Hauser-Davis L V de Freitas D S Cukierman W S Cruz M C Miotto J Landeira-Fernandez A A Valiente-Gabioud C O Fernández N A Rey

Metallomics

Laboratory of Organic Synthesis and Coordination Chemistry Applied to Biological Systems (LABSO-BIO), Department of Chemistry, Pontifical Catholic University of Rio de Janeiro (PUC-Rio), Rua Marquês de São Vicente, 225, Gávea, 22453-900, Rio de Janeiro, RJ, Brazil.

Published: May 2015

Disruptions of biometal-Aβ(1-40) interactions by an isoniazid-derived hydrazone, INHHQ, were demonstrated via in vitro NMR titrations. The compound has adequate theoretical BBB absorption properties, assessed by in silico studies. In vivo acute toxicity assays indicate that INHHQ is innocuous up to 300 mg kg(-1), showing potential as an anti-Alzheimer's drug.

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http://dx.doi.org/10.1039/c5mt00003c	DOI Listing

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