Synthesis and discovery of a novel pyrazole derivative as an inhibitor of apoptosis through modulating integrin beta4, ROS, and p53 levels in vascular endothelial cells.
Bioorg Med Chem
; 16(9): 5171-80, 2008 May 01.
Article
em En
| MEDLINE
| ID: mdl-18362074
ABSTRACT
Recently, pyrazole derivatives as high affinity and selective A2A adenosine receptor antagonists have been reported. But, so far, there are no reports about the inhibitory effects of multi-substituted pyrazole derivatives on apoptosis of vascular endothelial cells (VECs). In this study, we synthesized six pyrazole derivatives and characterized the structures of the compounds by IR, (1)H NMR, mass spectroscopy, and element analysis. The biology assay showed that a novel pyrazole derivative, ethyl 3-(o-chlorophenyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxylate (MPD) at low concentration (25muM) increased VECs viability and inhibited VECs apoptosis induced by deprivation of serum and FGF-2. During this process, the levels of integrin beta4, reactive oxygen species (ROS), and p53 were depressed obviously. The data suggested that MPD was a potential inhibitor of apoptosis associated with the signal pathway mediated by integrin beta4, ROS, and p53 in VECs.
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Base de dados:
MEDLINE
Assunto principal:
Pirazóis
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Proteína Supressora de Tumor p53
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Espécies Reativas de Oxigênio
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Apoptose
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Integrina beta4
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Células Endoteliais
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article