Antiprotozoal activity of jatrogrossidione from jatropha grossidentata and jatrophone from jatropha isabellii

The activity of jatrogrossidione, the main diterpene of Jatropha grossidentata and jatrophone from Jatropha Isabella was determined against Leishmania and Trypanosoma cruzi strains in vitro as well as against Leishmania amazonensis in vivo. Jatrogrossidione showed a strong in vitro leishmanicidal and trypanocidal activity with IC₁₀₀, of 0.75 and 1.5-5.0 μg/mL, respectively. Under similar conditions, the IC₁₀₀ of glucantime, ketoconazole and pentamidine towards Leishmania strains were >100, 50-100 and 1 μg/mL, respectively. The IC₅₀ of jatrogrossidione was <0.25 μg/mL against amastigote forms of Leishmania infecting macrophages, with toxicity at concentrations higher than 0.5 μg/mL. BALB/c mice infected with L. amazonensis strain PH 8 were treated 24 h after infection with jatrogrossidione and jatrophone for 13 consecutive days. Jatrophone at 25 mg/kg/day subcutaneously administered was significantly active (p<0.05) against the virulent strain PH 8 of L. amazonesis; it was more active than Glucantime at 112 mg Sb^v per kg/day. Subcutaneous administration of jatrophone, however, proved to be too toxic under our assay conditions. Assays of single local treatment on the footpad infection 2 weeks after inoculation of L. amazonensis indicated that jatrogrossidione and jatrophone were inactive at the selected doses.