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Artículo

Anti-Trypanosoma cruzi action of a new benzofuran derivative based on amiodarone structure

Pinto Martinez, Andrea; Hernández Rodríguez, Vanessa; Rodríguez Durán, Jessica JenirethIcon ; Hejchman, Elżbieta; Benaim, Gustavo
Fecha de publicación: 06/2018
Editorial: Academic Press Inc Elsevier Science
Revista: Experimental Parasitology
ISSN: 0014-4894
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Bioquímica y Biología Molecular

Resumen

Chagas disease is a neglected tropical affection caused by the protozoan parasite Trypanosoma cruzi. There is no current effective treatment since the only two available drugs have a limited efficacy and produce side effects. Thus, investigation efforts have been directed to the identification of new drug leads. In this context, Ca2+ regulating mechanisms have been postulated as targets for antiparasitic compounds, since they present paramount differences when compared to host cells. Amiodarone is an antiarrhythmic with demonstrated trypanocidal activity acting through the disruption of the parasite intracellular Ca2+ homeostasis. We now report the effect of a benzofuran derivative based on the structure of amiodarone on T. cruzi. This derivative was able to inhibit the growth of epimastigotes in culture and of amastigotes inside infected cells, the clinically relevant phase. We also show that this compound, similarly to amiodarone, disrupts Ca2+ homeostasis in T. cruzi epimastigotes, via two organelles involved in the intracellular Ca2+ regulation and the bioenergetics of the parasite. We demonstrate that the benzofuran derivative was able to totally collapse the membrane potential of the unique giant mitochondrion of the parasite and simultaneously produced the alkalinization of the acidocalcisomes. Both effects are evidenced by a large increase in the intracellular Ca2+ concentration of T. cruzi.
Palabras clave: Trypanosoma cruzi , amiodarone , Ca2+ , benzofuran
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Atribución-NoComercial-SinDerivadas 2.5 Argentina (CC BY-NC-ND 2.5 AR)
Identificadores
URI: http://hdl.handle.net/11336/100501
URL: https://www.sciencedirect.com/science/article/abs/pii/S0014489417305325
DOI: http://dx.doi.org/10.1016/j.exppara.2018.04.010
Colecciones
Articulos(INGEBI)
Articulos de INST.DE INVEST.EN ING.GENETICA Y BIOL.MOLECULAR "DR. HECTOR N TORRES"
Citación
Pinto Martinez, Andrea; Hernández Rodríguez, Vanessa; Rodríguez Durán, Jessica Jenireth; Hejchman, Elżbieta; Benaim, Gustavo; Anti-Trypanosoma cruzi action of a new benzofuran derivative based on amiodarone structure; Academic Press Inc Elsevier Science; Experimental Parasitology; 189; 6-2018; 8-15
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