Synthesis and analysis of novel analogues of dexrazoxane and its open-ring hydrolysis product for protection against anthracycline cardiotoxicity in vitro and in vivo

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11150%2F15%3A10312387" target="_blank" >RIV/00216208:11150/15:10312387 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11160/15:10312387

Výsledek na webu

<a href="http://pubs.rsc.org/en/content/articlehtml/2015/tx/c5tx00048c" target="_blank" >http://pubs.rsc.org/en/content/articlehtml/2015/tx/c5tx00048c</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/c5tx00048c" target="_blank" >10.1039/c5tx00048c</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis and analysis of novel analogues of dexrazoxane and its open-ring hydrolysis product for protection against anthracycline cardiotoxicity in vitro and in vivo

Popis výsledku v původním jazyce

Cardiotoxicity is a serious drawback of anthracycline anti-cancer drugs and dexrazoxane is the only cardioprotective agent with clinically established efficacy. Iron-mediated oxidative stress is traditionally believed to be the primary cause of anthracycline cardiotoxicity, and dexrazoxane-induced cardioprotection is attributed to iron chelating properties of its open ring metabolite, ADR-925, which may inhibit the oxidative injury. However, dexrazoxane is also a catalytic inhibitor of topoisomerase II(TOP2), and the role of oxidative stress in clinically relevant forms of cardiotoxicity has increasingly been questioned. In this study, novel analogues of dexrazoxane (MK-15, ES-5) and ADR-925 (KH-TA4, JR-159) were synthesized, and evaluated in vitro and in vivo. When examined in the leukemic cell line, HL-60, these novel analogues did not interfere with the anti-proliferative action of daunorubicin. In contrast to dexrazoxane, they had no anti-cancer effect on their own and the changes

Název v anglickém jazyce

Synthesis and analysis of novel analogues of dexrazoxane and its open-ring hydrolysis product for protection against anthracycline cardiotoxicity in vitro and in vivo

Popis výsledku anglicky

Cardiotoxicity is a serious drawback of anthracycline anti-cancer drugs and dexrazoxane is the only cardioprotective agent with clinically established efficacy. Iron-mediated oxidative stress is traditionally believed to be the primary cause of anthracycline cardiotoxicity, and dexrazoxane-induced cardioprotection is attributed to iron chelating properties of its open ring metabolite, ADR-925, which may inhibit the oxidative injury. However, dexrazoxane is also a catalytic inhibitor of topoisomerase II(TOP2), and the role of oxidative stress in clinically relevant forms of cardiotoxicity has increasingly been questioned. In this study, novel analogues of dexrazoxane (MK-15, ES-5) and ADR-925 (KH-TA4, JR-159) were synthesized, and evaluated in vitro and in vivo. When examined in the leukemic cell line, HL-60, these novel analogues did not interfere with the anti-proliferative action of daunorubicin. In contrast to dexrazoxane, they had no anti-cancer effect on their own and the changes

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2015

Kód důvěrnosti údajů

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

Název periodika

Toxicology Research

ISSN

2045-452X

e-ISSN

—

Svazek periodika

4

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

17

Strana od-do

1098-1114

Kód UT WoS článku

000356612300031

EID výsledku v databázi Scopus

2-s2.0-84935024620