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.

A novel isochroman derivative inhibited apoptosis in vascular endothelial cells through depressing the levels of integrin beta4, p53 and ROS.

A new derivative of isochroman, 7-(isopropoxymethyl)-5-phenyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isochromene (ISO-9), was synthesized in our laboratory. In this study, we investigated the effect of ISO-9 on the apoptosis induced by deprivation of serum and fibroblast growth factor-2 (FGF-2) in human umbilical vein vascular endothelial cells (HUVECs). The results of MTT assay showed that 40 microM ISO-9 prevented the reduction of cell viability induced by the deprivation of serum and FGF-2 at 24 h or 48 h, respectively.

Novel morpholin-3-one derivatives induced apoptosis and elevated the level of P53 and Fas in A549 lung cancer cells.

Previously, we found that nine kinds of new morpholin-3-one derivatives could inhibit the growth of A549 lung cancer cells in a dose-dependent manner, but how they performed their function remained unknown. In this paper, we studied the effects of the three more effective morpholin-3-one derivatives {4-(4-chlorophenyl)-6-((4-nitrophenoxy) methyl) morpholin-3-one (1); 6-(4-chlorophenoxy)-4-(4-methoxyphenyl) morpholin-3-one (2); and 6-((4-nitrophenoxy) methyl)-4-phenylmorpholin-3-one (3)} on the cell cycle distribution, apoptosis, and the level of P53 and Fas that are two kinds of important proteins in the regulation of A549 cell growth and apoptosis. According to the results of cell viability, we selected 40 microg/ml of morpholin-3-one derivatives as the most appropriate concentration for the following study.