Structure-Activity Relationships of Nitro-Substituted Aroylhydrazone Iron Chelators with Antioxidant and Antiproliferative Activities
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F18%3A10382598" target="_blank" >RIV/00216208:11160/18:10382598 - isvavai.cz</a>
Result on the web
<a href="http://pubs.acs.org/doi/10.1021/acs.chemrestox.7b00324" target="_blank" >http://pubs.acs.org/doi/10.1021/acs.chemrestox.7b00324</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.chemrestox.7b00324" target="_blank" >10.1021/acs.chemrestox.7b00324</a>
Alternative languages
Result language
angličtina
Original language name
Structure-Activity Relationships of Nitro-Substituted Aroylhydrazone Iron Chelators with Antioxidant and Antiproliferative Activities
Original language description
Aroylhydrazone iron chelators such as salicylaldehyde isonicotinoyl hydrazone (SIH) protect various cells against oxidative injury and display antineoplastic activities. Previous studies have shown that a nitro-substituted hydrazone, namely, NHAPI, displayed markedly improved plasma stability, selective antitumor activity, and moderate antioxidant properties. In this study, we prepared four series of novel NHAPI derivatives and explored their iron chelation activities, anti- or pro-oxidant effects, protection against model oxidative injury in the H9c2 cell line derived from rat embryonic cardiac myoblasts, cytotoxicities to the corresponding noncancerous H9c2 cells, and antiproliferative activities against the MCF-7 human breast adenocarcinoma and HL-60 human promyelocytic leukemia cell lines. Nitro substitution had both negative and positive effects on the examined properties, and we identified new structure-activity relationships. Naphthyl and biphenyl derivatives showed selective antiproliferative action, particularly in the breast adenocarcinoma MCF-7 cell line, where they exceeded the selectivity of the parent compound NHAPI. Of particular interest is a compound prepared from 2-hydroxy-5-methyl-3-nitroacetophenone and biphenyl-4-carbohydrazide, which protected cardiomyoblasts against oxidative injury at 1.8 +/- 1.2 mu M with 24-fold higher selectivity than SIH. These compounds will serve as leads for further structural optimization and mechanistic studies.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - 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
Result continuities
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)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Chemical Research in Toxicology
ISSN
0893-228X
e-ISSN
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Volume of the periodical
31
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
435-446
UT code for WoS article
000436030100004
EID of the result in the Scopus database
2-s2.0-85047428788