Anti-parasite activity of nucleoside analogues in Leishmania tropica promastigotes.
Many nucleoside analogs were screened for anti-protozoa activity on Leishmania tropica in an in vitro culture system. 3'-Deoxyinosine and several tubercidin derivatives were found to be potent inhibitors for growth of the promastigote form of L. tropica. EC50 value of 3'-deoxyinosine was 4.43 X 10(-7)M. This compound was remarkably less toxic towards mouse mammary tumor FM3A cells (EC50, 1.25 X 10(-4) M). 3'-Deoxyinosine is metabolized by Leishmania promastigote to give 3'-deoxyinosine-5'-monophosphate, 3'-deoxy-adenosine(cordycepin)-5'-mono, di-, and triphosphates. This means that Leishmania can aminate the 6-position of 3'-deoxyinosine-5'-monophosphate, thereby converting it into a highly toxic compound.
D000818:Animals; D000981:Antiprotozoal Agents; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D007288:Inosine / Q000031:analogs & derivatives / Q000633:toxicity; D007891:Leishmania / Q000187:drug effects* / Q000254:growth & development; D008325:Mammary Neoplasms, Experimental / Q000473:pathology; D051379:Mice; D012263:Ribonucleosides / Q000633:toxicity*; D013329:Structure-Activity Relationship
D000981:Antiprotozoal Agents; D012263:Ribonucleosides; D007288:Inosine; C012271:deoxyinosine