Arabinosyl-6-mercaptopurine and Arabinosyl-6-mercaptopurine-5′-phosphate

Abstract

Summary

Arabinosyl-6-mercaptopurine (Ara-6-MP), an effective inhibitor of the growth of the mouse tumors Ca755, Ehrlich and L1210, was incubated in fortified cellfree extracts of these tumor cells under conditions where 6-methylmercaptopurine riboside and inosine were converted to nucleotide. No nucleotide formation could be detected. In vivo experiments with L1210 cells and normal mouse tissues also indicated that no nucleotide was formed. The 5'-phosphate of Ara-6-MP, obtained by chemical synthesis, had no apparent effect on the cytidylate reductase of tumor cell extracts under conditions such that Ara-6-MP was inhibitory. It was concluded that Ara-6-MP, a “fradulent nucleoside,” is active as such and does not require conversion to nucleotide for activation.