In vitro activity of meglumine antimoniate, a pentavalent antimonial drug, on Leishmania promastigotes.

1. The activity of a pentavalent antimonial drug glucantime on the growth of promastigote forms of Leishmania strains involved in South American cutaneous and mucocutaneous leishmaniasis was investigated. A marked difference in susceptibility to glucantime among four different strains and cloned lines obtained from a single strain was observed. For the sensitive strains (L. braziliensis M2903 and L. guyanensis M1176), the cell growth was reduced in a dose-dependent manner for drug concentrations at a range of 0.23 to 23 mM. However, despite the relative sensitivity of the assay, no significant increase of effect was observed in the presence of higher drug concentrations. For the resistant strains (L. amazonensis M10996 and L. braziliensis LTB259) a dose-response line is obtained at a higher concentration range (20 mM to 70 mM). 2. The influence of the drug on surface properties, respiratory activity and incorporation of radiolabelled leucine by a sensitive strain -L. guyanensis M1176-was studied as an approach to its site of action. Despite the increased intensity of self-agglutination for cells growing in the presence of glucantime, no significant change was observed in electrophoretic mobility or Concanavalin A reactivity. Since the oxygen uptake of glucose-stimulated promastigotes was only slightly reduced in the presence of 23 mM glucantime at 28 degrees C, the reduction was not sufficient to explain the total growth inhibition observed. A significant decrease of 14C-leucine incorporation into the cold TCA-insoluble fraction of drug-treated cells was observed within the same concentration range that reduces promastigote growth.