3'-Deoxyinosine as an anti-leishmanial agent: the metabolism and cytotoxic effects of 3'-deoxyinosine in Leishmania tropica promastigotes.

3'-Deoxyinosine is a potent inhibitor for growth of the promastigote form of Leishmania tropica. In culture, EC50 value is 4.43 X 10(-7) M for the promastigote. On the other hand, it is less toxic towards mouse mammary tumor FM3A cells: EC50 value is 1.25 X 10(-4) M. 3'-Deoxyinosine is metabolized by Leishmania promastigote to give 3'-deoxyinosine-5'-monophosphate and 3'-deoxyadenosine(cordycepin)-5'-mono-, di-, and triphosphates. This metabolic conversion provides a mechanism for the parasite-selective toxicity of 3'-deoxyinosine: Leishmania can aminate the 6-position of 3'-deoxyinosine residue, thereby converting a less toxic nucleoside into the cordycepin nucleotides that are known to be highly toxic to cells.