Aroylhydrazone iron chelators: Tuning antioxidant and antiproliferative properties by hydrazide modifications

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F16%3A10328164" target="_blank" >RIV/00216208:11160/16:10328164 - isvavai.cz</a>

Result on the web

<a href="http://www.sciencedirect.com/science/article/pii/S0223523416303944" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0223523416303944</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejmech.2016.05.015" target="_blank" >10.1016/j.ejmech.2016.05.015</a>

Result language

angličtina

Original language name

Aroylhydrazone iron chelators: Tuning antioxidant and antiproliferative properties by hydrazide modifications

Original language description

Aroylhydrazones such as salicylaldehyde isonicotinoyl hydrazone (SIH) are tridentate iron chelators that may possess antioxidant and/or antineoplastic activities. Their main drawback, their low stability in plasma, has recently been partially overcome by exchanging the aldimine hydrogen for an unbranched alkyl group. In this study, ten analogs of methyl- and ethyl-substituted SIH derivatives with modified hydrazide scaffolds were synthesized to further explore their structure-activity relationships. Their iron-chelation efficiencies, anti- or pro-oxidant potentials, abilities to induce protection against model oxidative injury on the H9c2 cell line derived from rat embryonic cardiac tissue, cytotoxicities on the same H9c2 cells and antiproliferative activities on MCF-7 human breast adenocarcinoma and HL-60 human promyelotic leukemia cell lines were evaluated. Compounds derived from lipophilic naphthyl and biphenyl hydrazides displayed highly selective antiproliferative activities against both MCF-7 and HL-60 cell lines, and they showed markedly improved stabilities in plasma compared to SIH. Of particular interest is a hydrazone prepared from 2-hydroxypropiophenone and pyridazin-4-carbohydrazide that showed a considerable antiproliferative effect and protected cardiomyoblasts against oxidative stress with a five-fold higher selectivity compared to the parent compound SIH. Thus, this work highlighted new structure-activity relationships among antiproliferative and antioxidant aroylhydrazones and identified new lead compounds for further development.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FR - Pharmacology and apothecary chemistry

OECD FORD branch

—

Project

<a href="/en/project/GA13-15008S" target="_blank" >GA13-15008S: New potential cardioprotective agents: study of structure-activity relationships in various types of myocardial injury</a><br>

Continuities

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

Publication year

2016

Confidentiality

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

Name of the periodical

European Journal of Medicinal Chemistry

ISSN

0223-5234

e-ISSN

—

Volume of the periodical

120

Issue of the periodical within the volume

September

Country of publishing house

FR - FRANCE

Number of pages

14

Pages from-to

97-110

UT code for WoS article

000379102800009

EID of the result in the Scopus database

2-s2.0-84968836040