Dados do Trabalho

Título

Flau-A: A naphthoquinone derivative as potential therapeutic candidate against visceral leishmaniasis

Introdução

Visceral leishmaniasis (VL) is a critical public health problem in tropical and subtropical regions in the world. The current treatment has been hampered by the toxicity and/or high cost of drugs, as well as by emergence of parasite resistance. Therefore, the search for alternative antileishmanial candidates is urgent. Recently, a naphthoquinone derivative namely 2-(2,3,4-tri-O-acetyl-6-deoxy-β-L-galactopyranosyloxy)-1,4-naphthoquinone or Flau-A showed an effective in vitro biological action against Leishmania infantum.

Objetivo (s)

In this context, and following the rationale to identify new anti-leishmanial targets against VL; Flau-A was evaluated as therapeutic candidate against L. infantum infection in a murine model.

Material e Métodos

In this present study, the efficacy of Flau-A – pure form or incorporated into Poloxamer 407-based micelle (Flau-A/Mic) – was evaluated in L. infantum BALB/c mice (n = 12 per group). The products were administered subcutaneously in the infected animals, which were then euthanized one (n = 6 per group) and 15 (n = 6 per group) days post-therapy, when immunological, parasitological and toxicological parameters were investigated.

Resultados e Conclusão

Animals treated with the micellar composition induced the development of a specific antileishmanial Th1-type immune response, which was characterized by high levels of IFN-γ, IL-12, TNF-α, GM-CSF, and IgG2a isotype antibody. In addition, animals receiving free Flau-A and Flau-A/Mic presented also significant reductions in the parasite load in their spleens, livers, bone marrow and draining lymph nodes, when compared to data found in the control (saline and empty micelles) groups, in both periods of time; having the micellar composition presented better parasitological and immunological results than free Flau-A. In conclusion, the preliminary data suggest that this composition could be considered as a new candidate in future studies as a promising therapeutic candidate against VL.

Palavras-chave

visceral leishmaniasis, treatment, polymeric micelles, naphthoquinone derivative, immune response.

Agradecimentos

CAPES, CNPq and FAPEMIG.