Structure-Activity Relationships of Nitro-Substituted Aroylhydrazone Iron Chelators with Antioxidant and Antiproliferative Activities

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Structure-Activity Relationships of Nitro-Substituted Aroylhydrazone Iron Chelators with Antioxidant and Antiproliferative Activities

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Structure-Activity Relationships of Nitro-Substituted Aroylhydrazone Iron Chelators with Antioxidant and Antiproliferative Activities

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/GA13-15008S" target="_blank" >GA13-15008S: Nová potenciální kardioprotektiva: studium vztahů mezi chemickou strukturou a protektivním účinkem u různých typů poškození myokardu</a><br>

Návaznosti

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

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Chemical Research in Toxicology

ISSN

0893-228X

e-ISSN

—

Svazek periodika

31

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

435-446

Kód UT WoS článku

000436030100004

EID výsledku v databázi Scopus

2-s2.0-85047428788