title: 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.
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.
authors: Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China. bxzhao@sdu.edu.cn
authors: Bao-Xiang
authors: BX
authors: Zhao
authors: Lu
authors: L
authors: Zhang
authors: Xing-Shang
authors: XS
authors: Zhu
authors: Mao-Sheng
authors: MS
authors: Wan
authors: Jing
authors: J
authors: Zhao
authors: Yun
authors: Y
authors: Zhang
authors: Shang-Li
authors: SL
authors: Zhang
authors: Jun-Ying
authors: JY
authors: Miao
mesh_terms: 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
chemical_list: 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