Atividade biológica Antileishmanial in Vitro e in Vivo de uma molécula derivada de Cloroquinolina contra diferentes espécies de Leishmania

Abstract

The identification of new candidates for the treatment against leishmaniasis is necessary, since drugs currently available are toxic and/or expensive; making the search for safer, more effective and selective pharmaceutical options necessary. Efforts to develop new candidates based on known biological function molecule analogues have been an interesting strategy. In this context, quinoline derivatives have shown biological activity against distinct diseases. In the present study, a chloroquinoline derivative, namely “AM1009” [N1- (7-chloroquinolin-4-yl) -N3-cyclohexylpropane-1,3-diamine], was in vitro tested against two Leishmania species: Leishmania infantum and L. amazonensis, which are capable of causing visceral and integumentary leishmaniasis, respectively. Inhibitory concentrations on 50% of Leishmania promastigotes (EC50), murine macrophages (CC50) and in human red blood cells (RBC50) were evaluated. In addition, the treatment of infected macrophages and the inhibition of infection using pretreated parasites were also investigated. In the results, the molecule was highly effective against both parasite species, showing no significant toxicity, as well as it was also effective in the treatment of infected macrophages and in the inhibition of the infection by such cells. An in vivo therapeutic effect was found in BALB/c mice, which were previously infected with L. amazonensis promastigotes, and later treated with AM1009. In the evaluation of parasitological and immunological parameters in the infected and treated animals, results showed higher activity of AM1009 in the treatment of infected mice, when compared to data obtained in the control groups, among which amphotericin B was used; since AM1009-treated animals presented lower lesion mean diameter and parasite load in the infected tissue and organs, when compared to the other groups. In addition, a Th1-type immune response was found in such animals, which also presented low renal and hepatic toxicity. In conclusion, results suggest that AM1009 could be considered as a possible therapeutic target to be evaluated in future studies for the treatment against leishmaniasis.