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Inhibitors of Nucleoside Metabolism¹

A group of 143 compounds, consisting mainly of substituted purines, was tested as potential inhibitors of ribonucleoside metabolism; the screening system was the synthesis of inosine, in vitro, by erythrocytes from humans. A series of purine derivatives with particular substituent groups at positions 6 and 9 inhibited inosine synthesis by intact erythrocytes, but these compounds had no effect against the same reaction catalyzed by disrupted erythrocytes. Compounds that were inhibitory in the erythrocyte system also inhibited the uridine-supported synthesis of inosine by intact Ehrlich ascites tumor cells. The most effective inhibitors were 6-thioether derivatives of purine ribonucleoside or 2-aminopurine ribonucleoside.

¹ This investigation was supported by the Medical Research Council of Canada and by the National Cancer Institute of Canada.

² University of Alberta Cancer Research Unit (McEachern Laboratory) and Department of Biochemistry, Edmonton, Alberta.