New tirapazamine derivatives protect cardiomyocytes from doxorubicin toxicity

Current Issues in Pharmacy and Medical Sciences

Matosiuk Dariusz¹  Szacon Elzbieta¹  Rzadkowska Marzena¹  Sysa Marcin²  Ostrowska Marta²  Dudka Jaroslaw²  Iwan Magdalena³  Humeniuk Ewelina³  Korga Agnieszka³ 

[1] Department of Synthesis and Chemical Technology of Pharmaceutical Substances, Medical University of Lublin, Poland;Department of Toxicology, Medical University of Lublin, Poland;Independent Medical Biology Unit, Medical University of Lublin, Poland;

关键词: doxorubicin;    tirapazamine derivative;    cardiotoxicity;    triphenylphosphine cation;    oxidative stress;   

DOI  :  10.2478/cipms-2020-0001

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown