In vitro and in vivo studies on the activity and selectivity of butoconazole in experimental infection by Trypanosoma cruzi

Autores
Rodrigues Leite, Gabriela; da Gama Jaen Batista, Denise; Batista, Marcos Meuser; da Costa, Krislayne Nunes; Mac Loughlin, Tomas Mariano; Barrionuevo, Emilia Mercedes; Talevi, Alan; Aberca, Lucas N.; Moreira, Otacilio C.; Faier Pereira, Amanda; da Silva Ferreira, Beatriz Iandra; Correia Soeiro, Maria de Nazaré
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BACKGROUND The protozoan Trypanosoma cruzi causes Chagas disease (CD). There are two drugs available for the treatment with limited efficacy, especially in the later stage. Focusing on drug repurposing by virtual screening of chemical databases, butoconazole (BTZ) was identified as promising hit. OBJECTIVES Our aim was to explore the trypanosomicidal effect of BTZ alone or in combination with benznidazole (BZ) against T. cruzi. METHODS and FINDINGS Our in vitro assays validated the low cytotoxicity of BTZ and high potency on amastigotes (EC50 = 0.07 μM), being 24-fold more potent than BZ. Washout assays demonstrated the sterilisation capacity of BTZ, whereas its combination with BZ gave an additive interaction (xƩFICI = 0.66). In a mouse model of acute T. cruzi infection, BTZ was unable to suppress parasitaemia but ensured the animal survival. BTZ plus BZ reduced parasitaemia and provided higher survival rates than monotherapies. However, quantitative polymerase chain reaction (qPCR) revealed that BTZ + BZ protocol gave 100% of lack of parasitological cure, as parasite satDNA was amplified in the heart of all surviving animals. MAIN CONCLUSIONS Our dataset reinforces the relevance of drug repurposing and combination strategies to advance into the development of novel therapeutic approaches for CD.
Fil: Rodrigues Leite, Gabriela. Instituto Oswaldo Cruz ; Fundacion Oswaldo Cruz ; Ministerio de Salud de Brasil;
Fil: da Gama Jaen Batista, Denise. Instituto Oswaldo Cruz ; Fundacion Oswaldo Cruz ; Ministerio de Salud de Brasil;
Fil: Batista, Marcos Meuser. Instituto Oswaldo Cruz ; Fundacion Oswaldo Cruz ; Ministerio de Salud de Brasil;
Fil: da Costa, Krislayne Nunes. Instituto Oswaldo Cruz ; Fundacion Oswaldo Cruz ; Ministerio de Salud de Brasil;
Fil: Mac Loughlin, Tomas Mariano. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigaciones del Medio Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones del Medio Ambiente; Argentina
Fil: Barrionuevo, Emilia Mercedes. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina
Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Aberca, Lucas N.. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina
Fil: Moreira, Otacilio C.. Fundación Oswaldo Cruz; Brasil
Fil: Faier Pereira, Amanda. Fundación Oswaldo Cruz; Brasil
Fil: da Silva Ferreira, Beatriz Iandra. Fundación Oswaldo Cruz; Brasil
Fil: Correia Soeiro, Maria de Nazaré. Fundación Oswaldo Cruz; Brasil
Materia
Drug repurposing
Chagas disease
Butoconazole
Trypanosoma cruzi
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/282334
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/282334
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling In vitro and in vivo studies on the activity and selectivity of butoconazole in experimental infection by Trypanosoma cruziRodrigues Leite, Gabrielada Gama Jaen Batista, DeniseBatista, Marcos Meuserda Costa, Krislayne NunesMac Loughlin, Tomas MarianoBarrionuevo, Emilia MercedesTalevi, AlanAberca, Lucas N.Moreira, Otacilio C.Faier Pereira, Amandada Silva Ferreira, Beatriz IandraCorreia Soeiro, Maria de NazaréDrug repurposingChagas diseaseButoconazoleTrypanosoma cruzihttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1BACKGROUND The protozoan Trypanosoma cruzi causes Chagas disease (CD). There are two drugs available for the treatment with limited efficacy, especially in the later stage. Focusing on drug repurposing by virtual screening of chemical databases, butoconazole (BTZ) was identified as promising hit. OBJECTIVES Our aim was to explore the trypanosomicidal effect of BTZ alone or in combination with benznidazole (BZ) against T. cruzi. METHODS and FINDINGS Our in vitro assays validated the low cytotoxicity of BTZ and high potency on amastigotes (EC50 = 0.07 μM), being 24-fold more potent than BZ. Washout assays demonstrated the sterilisation capacity of BTZ, whereas its combination with BZ gave an additive interaction (xƩFICI = 0.66). In a mouse model of acute T. cruzi infection, BTZ was unable to suppress parasitaemia but ensured the animal survival. BTZ plus BZ reduced parasitaemia and provided higher survival rates than monotherapies. However, quantitative polymerase chain reaction (qPCR) revealed that BTZ + BZ protocol gave 100% of lack of parasitological cure, as parasite satDNA was amplified in the heart of all surviving animals. MAIN CONCLUSIONS Our dataset reinforces the relevance of drug repurposing and combination strategies to advance into the development of novel therapeutic approaches for CD.Fil: Rodrigues Leite, Gabriela. Instituto Oswaldo Cruz ; Fundacion Oswaldo Cruz ; Ministerio de Salud de Brasil;Fil: da Gama Jaen Batista, Denise. Instituto Oswaldo Cruz ; Fundacion Oswaldo Cruz ; Ministerio de Salud de Brasil;Fil: Batista, Marcos Meuser. Instituto Oswaldo Cruz ; Fundacion Oswaldo Cruz ; Ministerio de Salud de Brasil;Fil: da Costa, Krislayne Nunes. Instituto Oswaldo Cruz ; Fundacion Oswaldo Cruz ; Ministerio de Salud de Brasil;Fil: Mac Loughlin, Tomas Mariano. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigaciones del Medio Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones del Medio Ambiente; ArgentinaFil: Barrionuevo, Emilia Mercedes. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; ArgentinaFil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Aberca, Lucas N.. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; ArgentinaFil: Moreira, Otacilio C.. Fundación Oswaldo Cruz; BrasilFil: Faier Pereira, Amanda. Fundación Oswaldo Cruz; BrasilFil: da Silva Ferreira, Beatriz Iandra. Fundación Oswaldo Cruz; BrasilFil: Correia Soeiro, Maria de Nazaré. Fundación Oswaldo Cruz; BrasilFundação Oswaldo Cruz2025-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/282334Rodrigues Leite, Gabriela; da Gama Jaen Batista, Denise; Batista, Marcos Meuser; da Costa, Krislayne Nunes; Mac Loughlin, Tomas Mariano; et al.; In vitro and in vivo studies on the activity and selectivity of butoconazole in experimental infection by Trypanosoma cruzi; Fundação Oswaldo Cruz; Memórias do Instituto Oswaldo Cruz; 120; 5-2025; 1-181678-8060CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.scielo.br/j/mioc/a/phQGht9KrcgZczPW8LWRWcz/?lang=eninfo:eu-repo/semantics/altIdentifier/doi/10.1590/0074-02760240234info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-03-31T14:57:13Zoai:ri.conicet.gov.ar:11336/282334instacron: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:34982026-03-31 14:57:13.379CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv In vitro and in vivo studies on the activity and selectivity of butoconazole in experimental infection by Trypanosoma cruzi
title In vitro and in vivo studies on the activity and selectivity of butoconazole in experimental infection by Trypanosoma cruzi
spellingShingle In vitro and in vivo studies on the activity and selectivity of butoconazole in experimental infection by Trypanosoma cruzi
Rodrigues Leite, Gabriela
Drug repurposing
Chagas disease
Butoconazole
Trypanosoma cruzi
title_short In vitro and in vivo studies on the activity and selectivity of butoconazole in experimental infection by Trypanosoma cruzi
title_full In vitro and in vivo studies on the activity and selectivity of butoconazole in experimental infection by Trypanosoma cruzi
title_fullStr In vitro and in vivo studies on the activity and selectivity of butoconazole in experimental infection by Trypanosoma cruzi
title_full_unstemmed In vitro and in vivo studies on the activity and selectivity of butoconazole in experimental infection by Trypanosoma cruzi
title_sort In vitro and in vivo studies on the activity and selectivity of butoconazole in experimental infection by Trypanosoma cruzi
dc.creator.none.fl_str_mv Rodrigues Leite, Gabriela
da Gama Jaen Batista, Denise
Batista, Marcos Meuser
da Costa, Krislayne Nunes
Mac Loughlin, Tomas Mariano
Barrionuevo, Emilia Mercedes
Talevi, Alan
Aberca, Lucas N.
Moreira, Otacilio C.
Faier Pereira, Amanda
da Silva Ferreira, Beatriz Iandra
Correia Soeiro, Maria de Nazaré
author Rodrigues Leite, Gabriela
author_facet Rodrigues Leite, Gabriela
da Gama Jaen Batista, Denise
Batista, Marcos Meuser
da Costa, Krislayne Nunes
Mac Loughlin, Tomas Mariano
Barrionuevo, Emilia Mercedes
Talevi, Alan
Aberca, Lucas N.
Moreira, Otacilio C.
Faier Pereira, Amanda
da Silva Ferreira, Beatriz Iandra
Correia Soeiro, Maria de Nazaré
author_role author
author2 da Gama Jaen Batista, Denise
Batista, Marcos Meuser
da Costa, Krislayne Nunes
Mac Loughlin, Tomas Mariano
Barrionuevo, Emilia Mercedes
Talevi, Alan
Aberca, Lucas N.
Moreira, Otacilio C.
Faier Pereira, Amanda
da Silva Ferreira, Beatriz Iandra
Correia Soeiro, Maria de Nazaré
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Drug repurposing
Chagas disease
Butoconazole
Trypanosoma cruzi
topic Drug repurposing
Chagas disease
Butoconazole
Trypanosoma cruzi
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv BACKGROUND The protozoan Trypanosoma cruzi causes Chagas disease (CD). There are two drugs available for the treatment with limited efficacy, especially in the later stage. Focusing on drug repurposing by virtual screening of chemical databases, butoconazole (BTZ) was identified as promising hit. OBJECTIVES Our aim was to explore the trypanosomicidal effect of BTZ alone or in combination with benznidazole (BZ) against T. cruzi. METHODS and FINDINGS Our in vitro assays validated the low cytotoxicity of BTZ and high potency on amastigotes (EC50 = 0.07 μM), being 24-fold more potent than BZ. Washout assays demonstrated the sterilisation capacity of BTZ, whereas its combination with BZ gave an additive interaction (xƩFICI = 0.66). In a mouse model of acute T. cruzi infection, BTZ was unable to suppress parasitaemia but ensured the animal survival. BTZ plus BZ reduced parasitaemia and provided higher survival rates than monotherapies. However, quantitative polymerase chain reaction (qPCR) revealed that BTZ + BZ protocol gave 100% of lack of parasitological cure, as parasite satDNA was amplified in the heart of all surviving animals. MAIN CONCLUSIONS Our dataset reinforces the relevance of drug repurposing and combination strategies to advance into the development of novel therapeutic approaches for CD.
Fil: Rodrigues Leite, Gabriela. Instituto Oswaldo Cruz ; Fundacion Oswaldo Cruz ; Ministerio de Salud de Brasil;
Fil: da Gama Jaen Batista, Denise. Instituto Oswaldo Cruz ; Fundacion Oswaldo Cruz ; Ministerio de Salud de Brasil;
Fil: Batista, Marcos Meuser. Instituto Oswaldo Cruz ; Fundacion Oswaldo Cruz ; Ministerio de Salud de Brasil;
Fil: da Costa, Krislayne Nunes. Instituto Oswaldo Cruz ; Fundacion Oswaldo Cruz ; Ministerio de Salud de Brasil;
Fil: Mac Loughlin, Tomas Mariano. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigaciones del Medio Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones del Medio Ambiente; Argentina
Fil: Barrionuevo, Emilia Mercedes. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina
Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Aberca, Lucas N.. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina
Fil: Moreira, Otacilio C.. Fundación Oswaldo Cruz; Brasil
Fil: Faier Pereira, Amanda. Fundación Oswaldo Cruz; Brasil
Fil: da Silva Ferreira, Beatriz Iandra. Fundación Oswaldo Cruz; Brasil
Fil: Correia Soeiro, Maria de Nazaré. Fundación Oswaldo Cruz; Brasil
description BACKGROUND The protozoan Trypanosoma cruzi causes Chagas disease (CD). There are two drugs available for the treatment with limited efficacy, especially in the later stage. Focusing on drug repurposing by virtual screening of chemical databases, butoconazole (BTZ) was identified as promising hit. OBJECTIVES Our aim was to explore the trypanosomicidal effect of BTZ alone or in combination with benznidazole (BZ) against T. cruzi. METHODS and FINDINGS Our in vitro assays validated the low cytotoxicity of BTZ and high potency on amastigotes (EC50 = 0.07 μM), being 24-fold more potent than BZ. Washout assays demonstrated the sterilisation capacity of BTZ, whereas its combination with BZ gave an additive interaction (xƩFICI = 0.66). In a mouse model of acute T. cruzi infection, BTZ was unable to suppress parasitaemia but ensured the animal survival. BTZ plus BZ reduced parasitaemia and provided higher survival rates than monotherapies. However, quantitative polymerase chain reaction (qPCR) revealed that BTZ + BZ protocol gave 100% of lack of parasitological cure, as parasite satDNA was amplified in the heart of all surviving animals. MAIN CONCLUSIONS Our dataset reinforces the relevance of drug repurposing and combination strategies to advance into the development of novel therapeutic approaches for CD.
publishDate 2025
dc.date.none.fl_str_mv 2025-05
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/11336/282334
Rodrigues Leite, Gabriela; da Gama Jaen Batista, Denise; Batista, Marcos Meuser; da Costa, Krislayne Nunes; Mac Loughlin, Tomas Mariano; et al.; In vitro and in vivo studies on the activity and selectivity of butoconazole in experimental infection by Trypanosoma cruzi; Fundação Oswaldo Cruz; Memórias do Instituto Oswaldo Cruz; 120; 5-2025; 1-18
1678-8060
CONICET Digital
CONICET
url http://hdl.handle.net/11336/282334
identifier_str_mv Rodrigues Leite, Gabriela; da Gama Jaen Batista, Denise; Batista, Marcos Meuser; da Costa, Krislayne Nunes; Mac Loughlin, Tomas Mariano; et al.; In vitro and in vivo studies on the activity and selectivity of butoconazole in experimental infection by Trypanosoma cruzi; Fundação Oswaldo Cruz; Memórias do Instituto Oswaldo Cruz; 120; 5-2025; 1-18
1678-8060
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.scielo.br/j/mioc/a/phQGht9KrcgZczPW8LWRWcz/?lang=en
info:eu-repo/semantics/altIdentifier/doi/10.1590/0074-02760240234
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Fundação Oswaldo Cruz
publisher.none.fl_str_mv Fundação Oswaldo Cruz
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
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score 12.822162

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