Anti-parasite activity of nucleoside analogues: the metabolism of carbocyclic inosine in promastigotes of Leishmania tropica and Leishmania donovani and its activity against amastigotes of Leishmania donovani in vitro.
Carbocyclic inosine is a potent inhibitor for the growth of the promastigote form of Leishmania tropica and Leishmania donovani. In culture, the EC50 values of carbocyclic inosine are 8.3 X 10(-8) and 1.3 X 10(-7) M for the promastigotes of L. tropica and L. donovani, respectively. On the other hand, it is less toxic towards mouse mammary tumor FM3A cells: the EC50 value is 2.7 X 10(-4)M. Carbocyclic inosine is metabolized by Leishmania promastigotes to give carbocyclic adenosine-5'-triphosphate(aristeromycin-5'-triphosphate) and carbocyclic guanosine-5'-triphosphate. This metabolic conversion provides a mechanism for the parasite-selective toxicity of carbocyclic inosine. Carbocyclic inosine was found to be active against L. donovani amastigotes in an in vivo-like cultivation in vitro.
D000818:Animals; D000981:Antiprotozoal Agents / Q000378:metabolism*; D007288:Inosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D007893:Leishmania donovani / Q000187:drug effects / Q000378:metabolism*; D007895:Leishmania tropica / Q000378:metabolism*; D013045:Species Specificity
D000981:Antiprotozoal Agents; C047906:carbocyclic inosine; D007288:Inosine