Carbocyclic inosine as a potent anti-leishmanial agent: the metabolism and selective cytotoxic effects of carbocyclic inosine in promastigotes of Leishmania tropica and Leishmania donovani.
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.
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D007288:Inosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D007895:Leishmania tropica / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D014344:Trypanocidal Agents / Q000378:metabolism
D014344:Trypanocidal Agents; C047906:carbocyclic inosine; C030034:aristeromycin; D007288:Inosine; D000241:Adenosine