Estudo do mecanismo de ação e atividade terapêutica da naftoquinona LQB-166 na leishmaniose cutânea experimental

Abstract

Leishmaniasis are neglected diseases with different clinical outcomes and are caused by protozoa of the genus Leishmania. In Brazil, the main agent of cutaneous and mucosal leishmaniasis is Leishmania (Viannia) braziliensis. The current therapeutic arsenals available for these diseases are toxic, expensive and parasite resistance is a growing problem. Given this scenario it is necessary to expand the alternatives for treatment of leishmaniasis. Naphthoquinones are bioactive molecules with antitumor and antiprotozoal activities. The aim of this study was to evaluate the effect of the naphthoquinone LQB-166 (3-phenyl-lausone) on L. (V.) braziliensis in vitro and in experimental cutaneous leishmaniasis. LQB-166 showed a dosis and time-dependent activity in vitro on promastigotes and intracellular amastigotes (IC50 = 149 ± 13 μM) with low toxicity for human macrophages (CC50 = 2194 ± 74 µM). The treatment of macrophages with LQB-166 did not induce the nitric oxide production, but significantly increased the production of pro-inflammatory cytokines (IL-6, IL-12, IFN), anti-inflammatory (IL-10) and increased its phagocytic capacity. In vivo LQB-166 was capable of significantly decrease the parasite load (p<0,001) on golden hamsters treated by subcutaneous route or tattoo device. Moreover, Glucantime, a reference drug for leishmaniasis, was effective administered by tattoo device. These data show that LQB-166 has activity against L. (V.) braziliensis in vitro and in vivo, therefore it is a promising molecule to continued preclinical studies.