Flau-A, a naphthoquinone derivative, is a promising therapeutic candidate against visceral leishmaniasis : a preliminary study.
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2022
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Visceral leishmaniasis (VL) is a neglected tropical disease found in tropical and subtropical regions in the world.
The therapeutics used for the treatment against disease presents problems, mainly related to drug toxicity, route
of administration, high cost and/or by emergence of resistant strains. In this context, the search for alternative
antileishmanial candidates is desirable. 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. In the present study, the efficacy of this naphthoquinone derivative was evaluated in
an in vivo infection model. BALB/c mice (n = 12 per group) were infected and later received saline or were
treated with empty micelles (B/Mic), free Flau-A or it incorporated in Poloxamer 407-based micelles (Flau-A/
Mic). 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 and parasitological eval-
uations were performed. Results showed that animals treated with Flau-A or Flau-A/Mic produced significantly
higher levels of antileishmanial IFN-γ, IL-12, TNF-α, GM-CSF, nitrite and IgG2a isotype antibody, when compared
to data found in the control (saline and B/Mic) groups; which showed significantly higher levels of parasite-
specific IL-4, IL-10 and IgG1 antibody. In addition, animals receiving free Flau-A or Flau-A/Mic presented also
significant reductions in the parasite load in their spleens, livers, bone marrows and draining lymph nodes, when
compared to the controls. A low hepatic and renal toxicity was also found. Overall, Flau-A/Mic showed better
immunological and parasitological results, when compared to the use of free molecule. In conclusion, pre-
liminary data suggest that this composition could be considered in future studies as promising therapeutic
candidate against VL.
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Immune response, Naphthoquinone derivative, Visceral leishmaniasis, Polymeric micelles, Treatment
Citação
MENDONÇA, D. V. C. et al. Flau-A, a naphthoquinone derivative, is a promising therapeutic candidate against visceral leishmaniasis: a preliminary study. Experimental parasitology, v. 233, artigo 108205, fev. 2022. Disponível em: <https://www.sciencedirect.com/science/article/pii/S0014489421001429>. Acesso em: 11 out. 2022.