Evaluation of the activity and toxicity of thiosemicarbazones and semi-carbazones against Trypanosoma cruzi and Leishmania (L. ) amazonensis in vitro.

by de Araújo, Renata Oliveira

The available treatment for Chagas´ disease and leishmaniasis are not efficient and present a high toxicity. Synergistic effect have been demonstrated when reference drugs and new compounds were associated and used against these pathologies. Thiosemicarbazones (TS) and semi- carbazones (SC) are classes of compounds with important activity against several pathogens, including T. cruzi and Leishmania sp. In the present thesis the in vitro effects of three thiosemicarbazones [estiryl-thiosemicarbazone, (2-methoxy-estiryl)-thiosemicarbazone and (3-methoxy-4-hydroxy-estiryl) thiosemicarbazone] and [(2-methoxy-estiryl)-semicarbazone and (3-methoxy-4-hydroxy-estiryl) semicarbazone] were evaluated against T. cruzi and Leishmania (L.) amazonensis. Our results demonstrated an excellent antiparasitic activity of the majority of the compounds, and that thiosemicarbazones were more actives on trypomastigote forms of T. cruzi in relation to L.(L.) amazonensis promastigotes. We also observed that (2-methoxy-estiryl)-thiosemicarbazone was more effective against T. cruzi amastigotes within human macrophage culture, comparing to intracellular parasites lodged in mice peritoneal macrophage, infected in vitro. The assays of the association of test compounds with the reference drugs, Benznidazole (BZ) for T. cruzi and Pentamidine (PT) for L. (L.) amazonensis, showed an important potentiation of the trypanocidal and leishmanicidal action of TS and SC against T. cruzi and L. (L.) amazonensis, presenting low toxicity to the mammal cells. Our promising results reinforce the importance of the continuity of these studies, in order to identify new more efficient therapies for the treatment of Chagas´ disease and leishmaniasis.