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001-es BibID:BIBFORM058639
Első szerző:Gergely Szabolcs (kardiológus)
Cím:High throughput screening identifies a novel compound protecting cardiomyocytes from doxorubicin-induced damage / Szabolcs Gergely, Csaba Hegedűs, Petra Lakatos, Katalin Kovács, Renáta Gáspár, Tamás Csont, László Virág
Dátum:2015
Megjegyzések:Antracyclines are effective anti-tumor agents. One of the most commonly used antracyclines is doxorubicin, which can be successfully used to treat a diverse spectrum of tumors, including breast -, lung -, thyroid gland tumors and leukemias. Application of these drugs is limited mainly by their cardiotoxic effect, which is determined by a lifetime cumulative dose. As the processes that are responsible for tumor chemotherapy and cardiotoxicity are different, this may give a hope for eliminating the side effect without affecting the anti-tumor effect. In our recent work, 10 000 compounds of the Chembridge's Diverset compound library were screened to identify compounds that can protect H9C2 rat cardiomyocytes against doxorubicin-induced cell death. An MTT-based high throughput viability screening was performed followed by retesting of the hit compounds in a morphology-based assay. The most effective compound proved protective in DOX-treated primary rat cardiomyocytes and was further characterized to demonstrate that it significantly decreased doxorubicin-induced apoptotic and necrotic cell death, inhibited DOX-induced activation of JNK MAP kinase without having considerable radical scavenging effect or interfering with the antitumor effect of DOX. 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 DOXinduced injury.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Oxidative Medicine and Cellular Longevity 2015 (2015), p. 1-12. -
További szerzők:Hegedűs Csaba (1980-) (biokémikus, molekuláris biológus) Lakatos Petra (1985-) (Molekuláris biológus) Kovács Katalin (1978-) (biokémikus) Gáspár Renáta Csont Tamás Virág László (1965-) (biokémikus, sejtbiológus, farmakológus)
Pályázati támogatás:OTKA-K112336
OTKA
OTKA-PD83473
OTKA
TAMOP-4.2.1./B-09/1/KONV-2010-0007
TÁMOP
TAMOP 4.2.2.A-111/1/KONV-2012-0025
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TÁMOP-4.2.2/B-10/1-2010-0024
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TÁMOP-4.2.2.A-11/1/KONV-2012-0035
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Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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