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.
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.
Zhao
Bao-Xiang
BX
Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China. bxzhao@sdu.edu.cn
Zhang
Lu
L
Zhu
Xing-Shang
XS
Wan
Mao-Sheng
MS
Zhao
Jing
J
Zhang
Yun
Y
Zhang
Shang-Li
SL
Miao
Jun-Ying
JY
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D039663:Integrin beta4 / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects* / Q000378:metabolism
D039663:Integrin beta4; D011720:Pyrazoles; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C530900:ethyl 3-(o-chlorophenyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxylate; D004247:DNA