Synthesis and Preliminary Biological Evaluation of 1,3,5-Triazine Amino Acid Derivatives to Study Their MAO Inhibitors
Three series of 4,6-dimethoxy-, 4,6-dipiperidino- and 4,6-dimorpholino-1,3,5-triazin-2-yl) amino acid derivatives were synthesized and characterized. A preliminary study for their monoamine oxidase inhibitory activity showed that compounds 7, 18, and 25 had MAO-A inhibition activity comparable to that of the standard clorgyline, with apparently more selective inhibitory activity toward MAO-A than MAO-B and no significant acute toxicity.
Inhibition of tumor growth and neovascularization by an anti-gastric ulcer agent, irsogladine.
Irsogladine used clinically as an anti-gastric ulcer agent, at 10(-6)-10(-4)M, inhibited cell proliferation and tubular morphogenesis of vascular endothelial cells, but the proliferation of human epidermoid cancer or glioma cells was not inhibited by this drug, even at 10(-4)M. In vivo studies demonstrated that p.o. administration of irsogladine significantly inhibited tumor growth of human glioma cells in mice, and histological analysis showed a dramatic decrease of the neovascularization in the tumors. In mice transplanted with chambers containing human glioma cells or hepatic cancer cells, irsogladine also inhibited angiogenesis. These in vivo and in vitro assays demonstrate that irsogladine may be a unique and potent inhibitor of tumor angiogenesis.
Changes in cyclic AMP content of rat gastric mucosa induced by ulcerogenic stimuli--in relation to the antiulcer activity of irsogladine maleate.
Changes in the cyclic AMP (cAMP) content of the gastric mucosa induced by ulcerogenic stimuli were investigated in rats. Ligation of the pylorus for 5 hr produced no glandular mucosal lesion, but increased the cAMP content in the fundus and antrum. Aspirin produced glandular mucosal lesions in the pylorus-ligated rats and caused an increase of the cAMP content in the fundus and a decrease in the antrum. Irsogladine maleate (IM), an antiulcer agent, inhibited both the changes in the cAMP content and the mucosal damage induced by aspirin. IM increased the cAMP content in both regions, especially the antrum, in normal rats. Dibutyryl cAMP (dbcAMP) given orally prevented the gastric mucosal lesions induced by aspirin without affecting gastric secretion. These results suggest that 1) the changes in the cAMP content of the fundus and antrum induced by aspirin may be associated with the formation of glandular mucosal damage, 2) the antiulcer activity of IM may be related to an increase of the cAMP content in mucous cells, and 3) dbcAMP given orally may penetrate into the surface mucous cells and activate defensive functions. Thus, cAMP in the mucous cells may protect the gastric mucosa.