2,6-Dihydroxybenzaldehyde analogues of the iron chelator salicylaldehyde isonicotinoyl hydrazone: Increased hydrolytic stability and cytoprotective activity against oxidative stress

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F18%3A10382911" target="_blank" >RIV/00216208:11160/18:10382911 - isvavai.cz</a>

Result on the web

<a href="http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00165" target="_blank" >http://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00165</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.chemrestox.8b00165" target="_blank" >10.1021/acs.chemrestox.8b00165</a>

Result language

angličtina

Original language name

2,6-Dihydroxybenzaldehyde analogues of the iron chelator salicylaldehyde isonicotinoyl hydrazone: Increased hydrolytic stability and cytoprotective activity against oxidative stress

Original language description

Salicylaldehyde isonicotinoyl hydrazone (SIH) is a small molecule and lipophilic chelating agent that firmly binds ferric ions from the cellular labile iron pool and is able to protect various tissues against oxidative damage. Previously, SIH possessed the best ratio of cytoprotective efficiency to toxicity among various iron chelators, including the desferrioxamine, deferiprone, and deferasirox used in clinical practice. Here, we prepared a series of 2,6-dihydroxybenzaldehyde aroylhydrazones as SIH analogues with an additional hydroxyl group that can be involved in the chelation of metal ions. Compound JK-31 (2,6-dihydroxybenzaldehyde 4-chlorobenzohydrazone) showed the best cytoprotective efficiency among the studied compounds including SIH. This compound significantly protected H9c2 cardiomyoblast cells against oxidative stress induced by various pro-oxidants, such as hydrogen peroxide, tert-butyl hydroperoxide, paraquat, epinephrine, N-acetyl-p-benzoquinone imine (a toxic metabolite of paracetamol), and 6-hydroxydopamine. The exceptional cytoprotective activity of JK-31 was confirmed using epifluorescence microscopy, where JK-31-treated H9c2 cells maintained a higher mitochondrial inner membrane potential in the presence of a lethal dose of hydrogen peroxide than was observed with cells treated with SIH. Hence, this study demonstrates the deleterious role of free iron ions in oxidative injury and the potential of 2,6-dihydroxybenzaldehyde aroylhydrazones in the prevention of various types of cardiac injuries, highlighting the need for further investigations into these compounds.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Chemical Research in Toxicology

ISSN

0893-228X

e-ISSN

—

Volume of the periodical

31

Issue of the periodical within the volume

11

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

1151-1163

UT code for WoS article

000451245200009

EID of the result in the Scopus database

2-s2.0-85056299230