Discovery of ß-Carboline Derivatives as a Highly Potent Cardioprotectant against Myocardial Ischemia-Reperfusion Injury.
J Med Chem
; 64(13): 9166-9181, 2021 07 08.
Article
em En
| MEDLINE
| ID: mdl-34132541
ABSTRACT
Timely myocardial reperfusion salvages ischemic myocardium from infarction, whereas reperfusion itself induces cardiomyocyte death, which is called myocardial ischemia/reperfusion (MI/R) injury. Herein, ß-carboline derivative 17c was designed and synthesized with obvious myocardial protective activity for the first time. Pretreatment of 17c effectively protected the cardiomyocyte H9c2 cells from H2O2-induced lactate dehydrogenase leakage and restored the endogenous antioxidants, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Besides, 17c effectively protected the mitochondria through decreasing the reactive oxygen species overproduction and enhancing the mitochondrial membrane potential. As a result, 17c significantly reduced the necrosis of cardiomyocytes in H2O2-induced oxidative stress, which was more potent than polydatin. In MI/R injury rats, 17c pretreatment obviously increased the levels of SOD and GSH-Px and inhibited the apoptosis of cardiomyocytes. Through this way, the size of myocardial infarction was significantly reduced after MI/R injury in vivo, better than that of polydatin, suggesting that 17c is a promising cardioprotectant for the prevention of MI/R injury.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carbolinas
/
Traumatismo por Reperfusão Miocárdica
/
Substâncias Protetoras
/
Descoberta de Drogas
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article