Trifluralin, a dinitroaniline microtubule inhibitor currently in use as an herbicide, has been shown to inhibit the proliferation of Plasmodium falciparum, Trypanosoma brucei, and several species of Leishmania, in vitro. As a topical formulation, trifluralin is also effective in vivo (in BALB/c mice) against Leishmania major and Leishmania mexicana. Although trifluralin and other dinitroaniline herbicides show significant activity as antiparasitic compounds, disputed indications of potential carcinogenicity will probably limit advanced development of these substances. However, researchers have suggested that the activity of trifluralin is due to an impurity or contaminant, not to trifluralin itself. We have pursued this lead and identified the structure of the active impurity. This compound, chloralin, is 100 times more active than trifluralin. On the basis of its structure, we developed a rational structure-activity model for chloralin. Using this model, we have successfully predicted and tested active analogs in a Leishmania promastigote assay; thus, we have identified the putative mechanism of action of this class of drugs in Leishmania species. Potentially, this will allow the design of noncarcinogenic, active drugs.

The efficiency of terbinafine was tested in C57BL/6 mice inoculated with the Leishmania (Leishmania) amazonensis strain MHOM/BR/PH8. The mice were administered: terbinafine at a dose of 100mg/kg/d by via oral; 0.9% saline solution orally as the control; and subcutaneous sodium stibogluconate 400mg SbV/kg/d as gold standard, for 20 days. Terbinafine was demonstrated to be ineffective when compared to the controls, using clinical and parasitological parameters and the limiting dilution assay.