Organoselenium compounds that enhance fibrinolytic activity of vascular endothelial cells

<p>Because organometallic compounds can exhibit different reactivity with the organic framework structures and metals that compose them, the opportunities for the use of organometallic compounds are expanding. We have investigated the cytotoxicity of nucleophilic organometallic compounds using organoselenium and organotellurium compounds, and found that diphenyl selenide and diphenyl telluride have low cytotoxicity against vascular endothelial cells. In this study, we examined the effects of derivatives of these compounds, 2-[(N,N-dimethylamino)methyl]phenyl phenyl selenide (HU JK10-03) or 2-[(N,N-dimethylamino)methyl]phenyl phenyl telluride (HU JK10-09), on fibrinolytic activity. Both compounds showed no decrease in vascular endothelial cell viability under serum-containing culture conditions, but under serum-free culture conditions, HU JK10-09 decreased cell viability at 5 µM. The mRNA expression of t-PA, an activator of fibrinolysis, and PAI-1, an inhibitor of t-PA, in vascular endothelial cells was examined. The mRNA expression of t-PA mRNA was induced in a concentration-dependent manner only under treatment with HU JK10-03 and no significant effect on PAI-1 mRNA expression was observed under treatment with both compounds. In correlation with these results, fibrinolytic activity in the conditioned medium of the HU JK10-03-treated group was increased. This study found organometallic compounds that can modulate the fibrinolytic activity of vascular endothelial cells through the selection of the central metal.</p>