Atividade da pterocarpanoquinona LQB-182 em Leishmania.(V.) braziliensis

Abstract

Leishmaniasis are a complex of diseases with a wide spectrum of clinical manifestations caused by the genus Leishmania, which Leishmania. (Viannia.) braziliensis is the most distributed species in the New World. The therapeutic arsenal is restrict, toxic and expensive and facing this panorama, the search for new potential drugs becomes necessary. Pterocarpanquinones are synthetic hybrid molecules created from a naphthoquinone and pterocarpan. The aim of this study was to investigate in vitro and in vivo the activity of pterocarpanquinone LQB-182 against L. (V.) braziliensis. Our analysis in vitro showed LQB-182 activity on promastigotes (IC50=10,98 ± 1,44 µM), intracellular amastigotes (IC50 = 17,01±2,46µM) forms and low toxicity to BALB/c peritoneal macrophages (CC50 = 303,6 µM). The nitrite and reactive oxygen species quantification on culture supernatants showed that was no increase of production of this radicals. However, we observed that macrophages treated with LQB-182 phagocytosed more fluorescent beads than untreated controls (p<0,05). In vivo, LQB-182 was capable of controlling the lesion size and significantly decrease the parasite load (p<0,001) when administrated by intralesional route. The analysis of biochemical parameters showed an increase of hepatic enzymes, above the reference values. Preditive analisys of pharmakinetics parameters showed that LQB-182 has structural characteristics necessary to a good bioavailability whether administrated by oral route. This data show that pterocarpanquinone LQB-182 was selectively active in vitro against the parasite, and also effective in vivo. LQB-182 is a promising molecule to continue pre-clinical studies with the treatment of American cutaneous leishmaniasis caused by L. (V.) braziliensis