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

Autores
Pinto Martinez, Andrea; Hernández Rodríguez, Vanessa; Rodríguez Durán, Jessica Jenireth; Hejchman, Elżbieta; Benaim, Gustavo
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Pinto Martinez, Andrea. instituto de Estudios Avanzados; Venezuela
Fil: Hernández Rodríguez, Vanessa. instituto de Estudios Avanzados; Venezuela
Fil: Rodríguez Durán, Jessica Jenireth. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. instituto de Estudios Avanzados; Venezuela
Fil: Hejchman, Elżbieta. Medical University of Warsaw; Polonia
Fil: Benaim, Gustavo. Universidad Central de Venezuela; Venezuela
Materia
Trypanosoma cruzi
amiodarone
Ca2+
benzofuran
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/100501
Acceder
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Anti-Trypanosoma cruzi action of a new benzofuran derivative based on amiodarone structurePinto Martinez, AndreaHernández Rodríguez, VanessaRodríguez Durán, Jessica JenirethHejchman, ElżbietaBenaim, GustavoTrypanosoma cruziamiodaroneCa2+benzofuranhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Chagas 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.Fil: Pinto Martinez, Andrea. instituto de Estudios Avanzados; VenezuelaFil: Hernández Rodríguez, Vanessa. instituto de Estudios Avanzados; VenezuelaFil: Rodríguez Durán, Jessica Jenireth. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. instituto de Estudios Avanzados; VenezuelaFil: Hejchman, Elżbieta. Medical University of Warsaw; PoloniaFil: Benaim, Gustavo. Universidad Central de Venezuela; VenezuelaAcademic Press Inc Elsevier Science2018-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/100501Pinto 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; 8-150014-4894CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0014489417305325info:eu-repo/semantics/altIdentifier/doi/10.1016/j.exppara.2018.04.010info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:40:27Zoai:ri.conicet.gov.ar:11336/100501instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:40:27.697CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Anti-Trypanosoma cruzi action of a new benzofuran derivative based on amiodarone structure
title Anti-Trypanosoma cruzi action of a new benzofuran derivative based on amiodarone structure
spellingShingle Anti-Trypanosoma cruzi action of a new benzofuran derivative based on amiodarone structure
Pinto Martinez, Andrea
Trypanosoma cruzi
amiodarone
Ca2+
benzofuran
title_short Anti-Trypanosoma cruzi action of a new benzofuran derivative based on amiodarone structure
title_full Anti-Trypanosoma cruzi action of a new benzofuran derivative based on amiodarone structure
title_fullStr Anti-Trypanosoma cruzi action of a new benzofuran derivative based on amiodarone structure
title_full_unstemmed Anti-Trypanosoma cruzi action of a new benzofuran derivative based on amiodarone structure
title_sort Anti-Trypanosoma cruzi action of a new benzofuran derivative based on amiodarone structure
dc.creator.none.fl_str_mv Pinto Martinez, Andrea
Hernández Rodríguez, Vanessa
Rodríguez Durán, Jessica Jenireth
Hejchman, Elżbieta
Benaim, Gustavo
author Pinto Martinez, Andrea
author_facet Pinto Martinez, Andrea
Hernández Rodríguez, Vanessa
Rodríguez Durán, Jessica Jenireth
Hejchman, Elżbieta
Benaim, Gustavo
author_role author
author2 Hernández Rodríguez, Vanessa
Rodríguez Durán, Jessica Jenireth
Hejchman, Elżbieta
Benaim, Gustavo
author2_role author
author
author
author
dc.subject.none.fl_str_mv Trypanosoma cruzi
amiodarone
Ca2+
benzofuran
topic Trypanosoma cruzi
amiodarone
Ca2+
benzofuran
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
Fil: Pinto Martinez, Andrea. instituto de Estudios Avanzados; Venezuela
Fil: Hernández Rodríguez, Vanessa. instituto de Estudios Avanzados; Venezuela
Fil: Rodríguez Durán, Jessica Jenireth. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. instituto de Estudios Avanzados; Venezuela
Fil: Hejchman, Elżbieta. Medical University of Warsaw; Polonia
Fil: Benaim, Gustavo. Universidad Central de Venezuela; Venezuela
description 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.
publishDate 2018
dc.date.none.fl_str_mv 2018-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/100501
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
0014-4894
CONICET Digital
CONICET
url http://hdl.handle.net/11336/100501
identifier_str_mv 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
0014-4894
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0014489417305325
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.exppara.2018.04.010
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844613280389136384
score 13.070432

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