<abstract xmlns="http://www.w3.org/1999/xhtml"><p>Doxorubicin cardiotoxicity is caused by various mechanisms, most importantly by oxidative stress originating in the mitochondria. Tirapazamine is a hypoxia-activated anticancer experimental drug. Both drugs in normoxia conditions undergo univalent reduction, thus tirapazamine may compete with doxorubicin in univalent reduction enzyme uptake. Herein, tirapazamine derivatives consisted of drug molecules and alkyl chain-connected triphenylphosphine cations that bring about an accumulation in mitochondria. The aim of this study was to evaluate the interaction of newly synthesized tirapazamine derivatives with doxorubicin in rat cardiomyocytes via an vitro model. In the work, H9C2 cells were incubated with combinations of doxorubicin, tirapazamine and seven variants of tirapazamine derivatives. After 24 hours, cell viability was assessed using MTT assay and the results were confirmed by microscopic observation. Tirapazamine in all tested concentrations did not revealed significant protective activity to cardiomyocytes treated with doxorubicine. However, tirapazamine derivatives diminished the cytotoxic effect of doxorubicin regardless of concentration and alkyl chain length. Tirapazamine derivatives have shown protective effects in relation to cardiomyocytes treated with doxorubicin and the mechanism of this phenomenon must be confirmed.</p></abstract>

Doxorubicin cardiotoxicity is caused by various mechanisms, most importantly by oxidative stress originating in the mitochondria. Tirapazamine is a hypoxia-activated anticancer experimental drug. Both drugs in normoxia conditions undergo univalent reduction, thus tirapazamine may compete with doxorubicin in univalent reduction enzyme uptake. Herein, tirapazamine derivatives consisted of drug molecules and alkyl chain-connected triphenylphosphine cations that bring about an accumulation in mitochondria. The aim of this study was to evaluate the interaction of newly synthesized tirapazamine derivatives with doxorubicin in rat cardiomyocytes via an vitro model. In the work, H9C2 cells were incubated with combinations of doxorubicin, tirapazamine and seven variants of tirapazamine derivatives. After 24 hours, cell viability was assessed using MTT assay and the results were confirmed by microscopic observation. Tirapazamine in all tested concentrations did not revealed significant protective activity to cardiomyocytes treated with doxorubicine. However, tirapazamine derivatives diminished the cytotoxic effect of doxorubicin regardless of concentration and alkyl chain length. Tirapazamine derivatives have shown protective effects in relation to cardiomyocytes treated with doxorubicin and the mechanism of this phenomenon must be confirmed.

New tirapazamine derivatives protect cardiomyocytes from doxorubicin toxicity

Department of Synthesis and Chemical Technology of Pharmaceutical Substances

Current Issues in Pharmacy and Medical Sciences

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

{"article-title":"New tirapazamine derivatives protect cardiomyocytes from doxorubicin toxicity"}

Doxorubicin cardiotoxicity is caused by various mechanisms, most importantly by oxidative stress originating in the mitochondria. Tirapazamine is a...

New tirapazamine derivatives protect cardiomyocytes from doxorubicin toxicity

Published Online: Mar 27, 2020

Page range: 1 - 5

Received: Jun 13, 2019

Accepted: Sep 06, 2020

DOI: https://doi.org/10.2478/cipms-2020-0001

Keywords
doxorubicin, tirapazamine derivative, cardiotoxicity, triphenylphosphine cation, oxidative stress

© 2020 Agnieszka Korga et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

New tirapazamine derivatives protect cardiomyocytes from doxorubicin toxicity

Published Online: Mar 27, 2020

Page range: 1 - 5

Received: Jun 13, 2019

Accepted: Sep 06, 2020

DOI: https://doi.org/10.2478/cipms-2020-0001

Keywordsdoxorubicin, tirapazamine derivative, cardiotoxicity, triphenylphosphine cation, oxidative stress

© 2020 Agnieszka Korga et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Keywords
doxorubicin, tirapazamine derivative, cardiotoxicity, triphenylphosphine cation, oxidative stress