The in vitro inhibition of purine nucleotide biosynthesis by 2-beta-D-ribofuranosylthiazole-4-carboxamide

A series of C-glycosylthiazoles were tested as inhibitors of purine nucleotide biosynthesis in $\text{in}\text{vitro}$ cultures of Ehrlich ascites tumor cells. The thiazole C-nucleoside, 2-β-D-ribofuranosylthiazole-4-carboxamide, demonstrated the only significant activity of the series as a specific inhibitor of guanine nucleotide biosynthesis. At concentrations of 10–1000 μM the compound inhibits the activities of the enzymes IMP dehydrogenase and GDP kinase by 50–60% and 30–60%, respectively. The antiviral agent ribavirin demonstrated a similar pattern of enzyme inhibition at the same range of concentrations. The possible relevance of this inhibition to the recently discovered antitumor properties of 2-β-D-ribofuranosylthiazole-4-carboxamide is discussed.