ANTIPROTOZOAL ACTIVITY OF JATROGROSSIDIONE FROM JATROPHA-GROSSIDENTATA AND JATROPHONE FROM JATROPHA-ISABELLII

The activity of jatrogrossidione, the main diterpene of Jatropha gross identata and jatrophone from Jatropha isabellii was determined against Leishmania and Trypanosoma cruzi strains in vitro as well as against Leishmania amazonensis in vivo, Jatrogrossidione showed a strong in vi tro leishmanicidal and trypanocidal activity with IC100 of 0.75 and 1. 5-5.0 mu g/mL, respectively, Under similar conditions, the IC100 of gl ucantime, ketoconazole and pentamidine towards Leishmania strains were >100, 50-100 and 1 mu g/mL, respectively, The IC50 of jatrogrossidion e was <0.25 mu g/mL against amastigote forms of Leishmania infecting m acrophages, with toxicity at concentrations higher than 0.5 mu g/mL. B ALB/c mice infected with L. amazonensis strain PH 8 were treated 24 h after infection with jatrogrossidione and jatrophone for 13 consecutiv e days, Jatrophone at 25 mg/kg/day subcutaneously administered was sig nificantly active (p<0.05) against the virulent strain PH 8 of L. amaz onesis; it was more active than Glucantime at 112 mg Sb-v per kg/day, Subcutaneous administration of jatrophone, however, proved to be too t oxic under our assay conditions. Assays of single local treatment on t he footpad infection 2 weeks after inoculation of L. amazonensis indic ated that jatrogrossidione and jatrophone were inactive at the selecte d doses.