Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: UNIPROT:P04637 (
p53
)
77,613
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID: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. 1836 74
Based on some common structural features of known compounds interfering with
p53
pathways and our previously synthesized benzamides, we synthesized new ethyl 5-(4-substituted benzamido)-
1-phenyl-1H-pyrazole
-4-carboxylates 26a-c, ethyl 5-(4-substituted benzamido)-1-(pyridin-2-yl)-1H-pyrazole-4-carboxylates 27a-c and N-(1H-indazol-6-yl)-4-substituted benzamides 31a,b bearing in the 4 position of the benzamido moiety the 2-phenylpropanamido or 2-phenoxyacetamido or cinnamamido groups. A preliminary test to evaluate the antiproliferative activity against human lung carcinoma H292 cells highlighted how compound 26c showed the best activity. This last was therefore selected for further studies with the aim to find the mechanism of action. Compound 26c induces intrinsic apoptotic pathway by activating
p53
and is also able to activate TRAIL-inducing death pathway by promoting increase of DR4 and DR5 death receptors, downregulation of c-FLIP
L
and caspase-8 activation.
...
PMID:Novel 4-(3-phenylpropionamido), 4-(2-phenoxyacetamido) and 4-(cinnamamido) substituted benzamides bearing the pyrazole or indazole nucleus: synthesis, biological evaluation and mechanism of action. 3040 49
