3'-Deoxy-3'-fluoroinosine as a potent antileishmanial agent. The metabolism and selective cytotoxic effect of 3'-deoxy-3'-fluoroinosine against Leishmania tropica and L. donovani in vitro and in vivo.
We studied the antileishmanial activity of 3'-deoxy-3'-fluoroinosine (3'-FI) against Leishmania tropica and L. donovani. In in vitro cultivation, the EC50 values (the concentration of drug necessary to inhibit the growth rate of cells to 50% of the control value) obtained for 3'-FI against the promastigotes of L. tropica and L. donovani were 2.3 x 10(-7) and 1.0 x 10(-6) M, respectively. It was less toxic toward mouse mammary-tumor FM3A cells, a model host; the EC50 value was 1.9 x 10(-4) M. Leishmania promastigote metabolized 3'-FI to 3'-deoxy-3'-fluoroadenosine 5'-triphosphate (3'-FATP) but FM3A cells did not. 3'-FI was effective against L. donovani amastigotes in J774.1 cells in an in vitro cultivation system under conditions similar to those used in the in vivo assay. 3'-FI (50 mg/kg, given i.v.) showed a cytotoxic effect against the amastigotes of L. donovani in mice.
D000818:Animals; D000981:Antiprotozoal Agents / Q000378:metabolism* / Q000627:therapeutic use / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D007288:Inosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development; D007895:Leishmania tropica / Q000187:drug effects* / Q000254:growth & development; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013997:Time Factors
D000981:Antiprotozoal Agents; C070277:3'-deoxy-3'-fluoroinosine; D007288:Inosine