Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease

Autores
Sbaraglini, Maria Laura; Bellera, Carolina Leticia; Fraccaroli, Laura Virginia; Larocca, Luciana; Carrillo, Carolina; Talevi, Alan; Alba Soto, Catalina Dirney
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Despite current efforts worldwide to develop new medications against Chagas disease, only two drugs are available, nifurtimox and benznidazole. Both drugs require prolonged treatment and have multiple side effects and limited efficacy on adult patients chronically infected with Trypanosoma cruzi. Recently, computer-guided drug repositioning led to the discovery of the trypanocidal effects of clofazimine and benidipine. These compounds showed inhibitory effects on cruzipain, the major cysteine protease of T. cruzi, of different parasite stages and in a murine model of acute Chagas disease. The aim of this work was to determine the efficacy of these novel cruzipain inhibitors when administered in a murine model of chronic Chagas disease. Benidipine and clofazimine were able to reduce the parasite burden in cardiac and skeletal muscles of chronically infected mice compared with untreated mice as well as diminish the inflammatory process in these tissues. Further studies should be performed to study the synergism with benznidazole and nifurtimox in view of combined therapies.
Fil: Sbaraglini, Maria Laura. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bellera, Carolina Leticia. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fraccaroli, Laura Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología ; Argentina
Fil: Larocca, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología ; Argentina
Fil: Carrillo, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología ; Argentina
Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Alba Soto, Catalina Dirney. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Materia
Benidipine
Chagas Disease
Chronic Phase
Clofazimine
Drug Repositioning
Trypanosoma Cruzi
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:11336/38941
Acceder
id CONICETDig_457b3669884e68b935336b515143efce
oai_identifier_str oai:ri.conicet.gov.ar:11336/38941
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Novel cruzipain inhibitors for the chemotherapy of chronic Chagas diseaseSbaraglini, Maria LauraBellera, Carolina LeticiaFraccaroli, Laura VirginiaLarocca, LucianaCarrillo, CarolinaTalevi, AlanAlba Soto, Catalina DirneyBenidipineChagas DiseaseChronic PhaseClofazimineDrug RepositioningTrypanosoma Cruzihttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Despite current efforts worldwide to develop new medications against Chagas disease, only two drugs are available, nifurtimox and benznidazole. Both drugs require prolonged treatment and have multiple side effects and limited efficacy on adult patients chronically infected with Trypanosoma cruzi. Recently, computer-guided drug repositioning led to the discovery of the trypanocidal effects of clofazimine and benidipine. These compounds showed inhibitory effects on cruzipain, the major cysteine protease of T. cruzi, of different parasite stages and in a murine model of acute Chagas disease. The aim of this work was to determine the efficacy of these novel cruzipain inhibitors when administered in a murine model of chronic Chagas disease. Benidipine and clofazimine were able to reduce the parasite burden in cardiac and skeletal muscles of chronically infected mice compared with untreated mice as well as diminish the inflammatory process in these tissues. Further studies should be performed to study the synergism with benznidazole and nifurtimox in view of combined therapies.Fil: Sbaraglini, Maria Laura. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bellera, Carolina Leticia. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fraccaroli, Laura Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología ; ArgentinaFil: Larocca, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología ; ArgentinaFil: Carrillo, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología ; ArgentinaFil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alba Soto, Catalina Dirney. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaElsevier Science2016-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/38941Sbaraglini, Maria Laura; Bellera, Carolina Leticia; Fraccaroli, Laura Virginia; Larocca, Luciana; Carrillo, Carolina; et al.; Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease; Elsevier Science; International Journal of Antimicrobial Agents; 48; 1; 7-2016; 91-950924-8579CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ijantimicag.2016.02.018info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0924857916300607info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:52:31Zoai:ri.conicet.gov.ar:11336/38941instacron: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:34982025-09-03 09:52:31.854CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease
title Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease
spellingShingle Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease
Sbaraglini, Maria Laura
Benidipine
Chagas Disease
Chronic Phase
Clofazimine
Drug Repositioning
Trypanosoma Cruzi
title_short Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease
title_full Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease
title_fullStr Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease
title_full_unstemmed Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease
title_sort Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease
dc.creator.none.fl_str_mv Sbaraglini, Maria Laura
Bellera, Carolina Leticia
Fraccaroli, Laura Virginia
Larocca, Luciana
Carrillo, Carolina
Talevi, Alan
Alba Soto, Catalina Dirney
author Sbaraglini, Maria Laura
author_facet Sbaraglini, Maria Laura
Bellera, Carolina Leticia
Fraccaroli, Laura Virginia
Larocca, Luciana
Carrillo, Carolina
Talevi, Alan
Alba Soto, Catalina Dirney
author_role author
author2 Bellera, Carolina Leticia
Fraccaroli, Laura Virginia
Larocca, Luciana
Carrillo, Carolina
Talevi, Alan
Alba Soto, Catalina Dirney
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Benidipine
Chagas Disease
Chronic Phase
Clofazimine
Drug Repositioning
Trypanosoma Cruzi
topic Benidipine
Chagas Disease
Chronic Phase
Clofazimine
Drug Repositioning
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 Despite current efforts worldwide to develop new medications against Chagas disease, only two drugs are available, nifurtimox and benznidazole. Both drugs require prolonged treatment and have multiple side effects and limited efficacy on adult patients chronically infected with Trypanosoma cruzi. Recently, computer-guided drug repositioning led to the discovery of the trypanocidal effects of clofazimine and benidipine. These compounds showed inhibitory effects on cruzipain, the major cysteine protease of T. cruzi, of different parasite stages and in a murine model of acute Chagas disease. The aim of this work was to determine the efficacy of these novel cruzipain inhibitors when administered in a murine model of chronic Chagas disease. Benidipine and clofazimine were able to reduce the parasite burden in cardiac and skeletal muscles of chronically infected mice compared with untreated mice as well as diminish the inflammatory process in these tissues. Further studies should be performed to study the synergism with benznidazole and nifurtimox in view of combined therapies.
Fil: Sbaraglini, Maria Laura. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bellera, Carolina Leticia. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fraccaroli, Laura Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología ; Argentina
Fil: Larocca, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología ; Argentina
Fil: Carrillo, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología ; Argentina
Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Alba Soto, Catalina Dirney. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
description Despite current efforts worldwide to develop new medications against Chagas disease, only two drugs are available, nifurtimox and benznidazole. Both drugs require prolonged treatment and have multiple side effects and limited efficacy on adult patients chronically infected with Trypanosoma cruzi. Recently, computer-guided drug repositioning led to the discovery of the trypanocidal effects of clofazimine and benidipine. These compounds showed inhibitory effects on cruzipain, the major cysteine protease of T. cruzi, of different parasite stages and in a murine model of acute Chagas disease. The aim of this work was to determine the efficacy of these novel cruzipain inhibitors when administered in a murine model of chronic Chagas disease. Benidipine and clofazimine were able to reduce the parasite burden in cardiac and skeletal muscles of chronically infected mice compared with untreated mice as well as diminish the inflammatory process in these tissues. Further studies should be performed to study the synergism with benznidazole and nifurtimox in view of combined therapies.
publishDate 2016
dc.date.none.fl_str_mv 2016-07
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/11336/38941
Sbaraglini, Maria Laura; Bellera, Carolina Leticia; Fraccaroli, Laura Virginia; Larocca, Luciana; Carrillo, Carolina; et al.; Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease; Elsevier Science; International Journal of Antimicrobial Agents; 48; 1; 7-2016; 91-95
0924-8579
CONICET Digital
CONICET
url http://hdl.handle.net/11336/38941
identifier_str_mv Sbaraglini, Maria Laura; Bellera, Carolina Leticia; Fraccaroli, Laura Virginia; Larocca, Luciana; Carrillo, Carolina; et al.; Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease; Elsevier Science; International Journal of Antimicrobial Agents; 48; 1; 7-2016; 91-95
0924-8579
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ijantimicag.2016.02.018
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0924857916300607
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
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv 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
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score 12.885934

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