tiazofurin and Carcinoma--Ehrlich-Tumor

AMP deaminase has a key position in regulation of the pool of adenine nucleotides and energetics in malignant cells. The aim of this investigation was to elucidate mechanism of regulation of activity of AMP deaminase in intact tumor cells. Using tiazofurin, which profoundly decreases the level of GTP, and guanosine which markedly increases its concentration in the Ehrlich ascites tumor cells under aerobic conditions, we have shown that this nucleotide is probably the major regulator of AMP deaminase activity in situ. This regulation, however, should be considered in relation to the time and the changes which occur during transition of the cells from aerobic to anaerobic phase, and reverse, when other factors, like concentrations of the substrate and ATP are involved.

Topics: AMP Deaminase; Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Guanosine; Guanosine Triphosphate; Liver Neoplasms, Experimental; Mice; Rats; Rats, Sprague-Dawley; Ribavirin; Tumor Cells, Cultured

A general reaction of glycosyl cyanides with liquid hydrogen sulfide in the presence of 4-dimethylaminopyridine to provide the corresponding glycosylthiocarboxamides is described. These glycosylthiocarboxamides were utilized as the precursors for the synthesis of 2-D-ribofuranosylthiazole-4-carboxamide and 2-beta-D-ribofuranosylthiazole-5-carboxamide (23). The structural modification of 2-beta-D-ribofuranosylthiazole-4-carboxamide (12) into 2-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)thiazole-4-carboxamide (15), 2-beta-D-ribofuranosylthiazole-4-thiocarboxamide (17), and 2-(5-deoxy-beta-D-ribofuranosyl)thiazole-4-carboxamide (19) is also described. These thiazole nucleosides were tested for in vitro activity against type 1 herpes virus, type 3 parainfluenza virus, and type 13 rhinovirus and an in vivo experiment was run against parainfluenza virus. They were also evaluated as potential inhibitors of purine nucleotide biosynthesis. It was shown that the compounds (12 and 15) which possessed the most significant antiviral activity were also active inhibitors (40-70%) of guanine nucleotide biosynthesis.

Topics: Animals; Antiviral Agents; Carcinoma, Ehrlich Tumor; Cells, Cultured; Cytopathogenic Effect, Viral; Female; Mice; Parainfluenza Virus 3, Human; Paramyxoviridae Infections; Purine Nucleotides; Rhinovirus; Ribavirin; Ribonucleosides; Simplexvirus; Structure-Activity Relationship; Thiazoles