Estudo in vitro da atividade anti-leishmana de compostos sintéticos derivados de terpenos e alcaloides contra diferentes espécies de leishmana

Abstract

Leishmaniasis is an endemic parasitic disease in tropical regions that is caused by protozoa of Leishmania genus transmitted by phlebotomine vectors. The clinical manifestations can vary on cutaneous, mucocutaneous or visceral form. Leishmaniasis presents high morbidity and mortality rates involved, which justifies the search for new therapeutic strategies, because the current therapies consist on use of toxic drugs and that has been inducing acquisition of resistance by the parasites. The aim of this work was to study the effects of natural or synthetic compounds related with secondary metabolism of plants, including Metha crispa hydroalcoholic extract, monoterpene rotundifolone, peryl alcohol monoterpene derivatives and piplartin analogs, a biologically active amide, in Leishmania donovani, Leishmania amazonensis and Leishmania infantum strains, which cause visceral and tegumentary leishmaniasis. A total of 36 substances were screened in different concentrations to evaluate their leishmanicidal potential in vitro, so, it was selected the compound that had a lower IC50 against L. donovani promastigote forms, to test their toxicity against human blood cells. Amphotericin B was used as a positive control and all experiments were performed in triplicate. In the present study, we demonstrated a variety of action levels of the compounds against different parasite species, with a better activity of 8,9-epoxyperialdehyde (EP-2), with good IC50 values (3 , 87 ± 0.8) compared with Amphotericin B (IC50 = 0.766 ± 0.06), but the first did not induce toxicity in red blood cells and peripheral blood mononuclear cells of healthy individuals. This results suggest good leishmanicidal action and advantage as regards its safety, that encourage the molecular mechanisms of action investigation of that substance, as well the necessity of more advanced toxicity tests to prove its efficacy in order, to introduce EP-2 as a possible adjuvant drug for leishmaniasis treatment.