Antileishmanial activity of a naphthoquinone derivate against promastigote and amastigote stages of Leishmania infantum and Leishmania amazonensis and its mechanism of action against L. amazonensis species

Débora Vasconcelos Costa Mendonça, Daniela Pagliara Lage, Stephane Lima Calixto, Flaviano Melo Ottoni, Grasiele de Sousa Vieira Tavares, Fernanda Ludolf, Miguel Angel Chávez-Fumagalli, Mônica Santos Schneider, Mariana Costa Duarte, Carlos Alberto Pereira Tavares, Ricardo José Alves, Elaine Soares Coimbra, Eduardo Antonio Ferraz Coelho

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

26 Citas (Scopus)

Resumen

Leishmaniasis has become a significant public health issue in several countries in the world. New products have been identified to treat against the disease; however, toxicity and/or high cost is a limitation. The present work evaluated the antileishmanial activity of a new naphthoquinone derivate, Flau-A [2-(2,3,4-tri-O-acetyl-6-deoxy-β-L-galactopyranosyloxy)-1,4-naphthoquinone], against promastigote and amastigote-like stages of Leishmania amazonensis and L. infantum. In addition, the cytotoxicity in murine macrophages and human red cells was also investigated. The mechanism of action of Flau-A was assessed in L. amazonensis as well as its efficacy in treating infected macrophages and inhibiting infection of pretreated parasites. Results showed that Flau-A was effective against promastigotes and amastigote-like forms of both parasite species, as well as showed low toxicity in mammalian cells. Results also highlighted the morphological and biochemical alterations induced by Flau-A in L. amazonensis, including loss of mitochondrial membrane potential, as well as increased reactive oxygen species production, cell shrinkage, and alteration of the plasma membrane integrity. The present study demonstrates for the first time the antileishmanial activity of Flau-A against two Leishmania species and suggests that the mitochondria of the parasites may be the main target organelle. Data shown here encourages the use of this molecule in new studies concerning treatment against Leishmania infection in mammalian hosts.

Idioma originalInglés
Páginas (desde-hasta)391-403
Número de páginas13
PublicaciónParasitology Research
Volumen117
N.º2
DOI
EstadoPublicada - 1 feb. 2018
Publicado de forma externa

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