Deazainosine was prepared by deamination of the antibiotic deazaadenosine (tubercidin). Whereas tubercidin inhibited the growth of Streptococcus faecalis, deazainosine was inactive against this organism. In contrast, both nucleoside analogs inhibited the growth of Sarcoma 180 cells in vitro and Ehrlich ascites and leukemia P388 cells in vivo. The lack of activity against S. faecalis is accompanied by the inability of the organism to convert deazainosine to tubercidin derivatives. Since the sensitive mammalian cells do carry out the amination reaction, this metabolic conversion appears to be required for biologic activity. A comparative evaluation of the antitumor activity of the two compounds showed that approximately 0.25–0.5 mg/kg of tubercidin produced the same effect as 4–8 mg/kg of deazainosine. This difference in potency may reflect the rate at which the conversion of deazainosine to tubercidin nucleotides occurs in sensitive cells. The more limited spectrum of tissue toxicity of deazainosine as compared to tubercidin may result from differences in the capacity of the tissues to carry out the metabolic conversion.
This study was aided by Grant T-436 from the American Cancer Society and by Grant CA-04130 from the National Cancer Institute, USPHS.