3'-DEOXY-3'-FLUOROINOSINE AS A PATENT ANTILEISHMANIAL AGENT - THE METABOLISM AND SELECTIVE CYTOTOXIC EFFECT OF 3'-DEOXY-3'-FLUOROINOSINE AGAINST LEISHMANIA-TROPICA AND LEISHMANIA-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 cultiva tion, the EC(50) values (the concentration of drug necessary to inhibi t the growth rate of cells to 50% of the control value) obtained for 3 '-FI against the promastigotes of L. tropica and L. danovani were 2.3 x 10(-7) and 1.0 x 10(-6) M, respectively. It was less toxic toward mo use mammary-tumor FM3A cells, a model host; the EC(50) value was 1.9 x 10(-4) M. Leishmania promastigote metabolized 3'-FI to 3'-deoxy-3'-fl uoroadenosine 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 th e in vivo assay. 3'-FI (50 mg/kg, given i.v.) showed a cytotoxic effec t against the amastigotes oft. donovani in mice.