Unknown

Dataset Information

0

High Throughput Screening Identifies a Novel Compound Protecting Cardiomyocytes from Doxorubicin-Induced Damage.


ABSTRACT: Antracyclines are effective antitumor agents. One of the most commonly used antracyclines is doxorubicin, which can be successfully used to treat a diverse spectrum of tumors. Application of these drugs is limited by their cardiotoxic effect, which is determined by a lifetime cumulative dose. We set out to identify by high throughput screening cardioprotective compounds protecting cardiomyocytes from doxorubicin-induced injury. Ten thousand compounds of ChemBridge's DIVERSet compound library were screened to identify compounds that can protect H9C2 rat cardiomyocytes against doxorubicin-induced cell death. The most effective compound proved protective in doxorubicin-treated primary rat cardiomyocytes and was further characterized to demonstrate that it significantly decreased doxorubicin-induced apoptotic and necrotic cell death and inhibited doxorubicin-induced activation of JNK MAP kinase without having considerable radical scavenging effect or interfering with the antitumor effect of doxorubicin. In fact the compound identified as 3-[2-(4-ethylphenyl)-2-oxoethyl]-1,2-dimethyl-1H-3,1-benzimidazol-3-ium bromide was toxic to all tumor cell lines tested even without doxorubicine treatment. This benzimidazole compound may lead, through further optimalization, to the development of a drug candidate protecting the heart from doxorubicin-induced injury.

SUBMITTER: Gergely S 

PROVIDER: S-EPMC4475553 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

altmetric image

Publications

High Throughput Screening Identifies a Novel Compound Protecting Cardiomyocytes from Doxorubicin-Induced Damage.

Gergely Szabolcs S   Hegedűs Csaba C   Lakatos Petra P   Kovács Katalin K   Gáspár Renáta R   Csont Tamás T   Virág László L  

Oxidative medicine and cellular longevity 20150607


Antracyclines are effective antitumor agents. One of the most commonly used antracyclines is doxorubicin, which can be successfully used to treat a diverse spectrum of tumors. Application of these drugs is limited by their cardiotoxic effect, which is determined by a lifetime cumulative dose. We set out to identify by high throughput screening cardioprotective compounds protecting cardiomyocytes from doxorubicin-induced injury. Ten thousand compounds of ChemBridge's DIVERSet compound library wer  ...[more]

Similar Datasets

| S-EPMC5807538 | biostudies-literature
| S-EPMC3914678 | biostudies-literature
| S-EPMC10492798 | biostudies-literature
| S-EPMC3660563 | biostudies-literature
| S-EPMC7034061 | biostudies-literature
| S-EPMC4089024 | biostudies-literature
| S-EPMC3583499 | biostudies-literature
| S-EPMC2878863 | biostudies-other
| S-EPMC6361972 | biostudies-literature
| S-EPMC7386506 | biostudies-literature