Avaliação da atividade leishmanicida no contexto in vivode compostos análogos da miltefosina

Abstract

Pentavalent antimonials are the gold standart treatment drugs of Leishmaniasis in Brazil, witch are beign used for over 40 years until now and no longer is able to control the Visceral Leishmaniasis (LV) in the world. The use of alternative drugs as Amphothericin B, Pentamidine and Miltefosine have been used as a new strategy against the LV. In this context, the synthesis of new compounds by bioisosterism has grown in use. The main goal of this study is to evaluate a possible therapeutic potencial of Alkyltriazole (C11) and Alkylphosphocholine (C4) which are both analogs of Miltefosine, in golden hamsters (Mesocricetus auratus) infected with L. (L.) infantum chagasi. The animals were infected intraperiatoneally with 1x107 amastigotes and submitted to the treatment of C11 and C4 within a concentration of 25mg/kg by gavage and 50mg/kg of intraperitoneal Glucantime (GLU). At the end of the treatment, the animals were euthanized and fragments of liver and spleen were collected to the quantification of parasitary load by qPCR; histopathological analysis and expression of IL-10, IL-4, IL-17, TNF-α, TGF-β, INF-Υ citokines by qPCR in the spleen. The animals treated with C11 and C4 did not present a statistical significant reduction of parasitary load when compared with the infected and non treated group (INT) (p<0,05). Remarkably it was possible to notice that there was no significative difference between C11 and GLU groups in the liver (p<0.05). Histologically the animals treated with C11 have shown a greater conservation in the White Pulp (PB) and Red Pulp (PV) ratio, keeping more than 50% of the white pulp as opposed with 9% of the INT group. The citokines analisys showed and interesting relation of the immunologic response in the C11 group, were we note an increased expression of IL-17 and TNF-α and a decrease in expression of IL-10 faced with the INT results. This data indicates that C11 could be and interesting compound against the LV, since the promising results against the disease.