Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effects

Autores
Bellera, Carolina Leticia; Balcazar, Dario Emmanuel; Alberca, Lucas Nicolás; Labriola, Carlos Alberto; Talevi, Alan; Carrillo, Carolina
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cruzipain (Cz) is the major cystein protease of the protozoan Trypanosoma cruzi, etiological agent of Chagas disease. From a 163-compound dataset, a 2D-classifier capable of identifying Cz inhibitors was obtained and applied in a virtual screening campaign on the DrugBank database, which compiles FDA-approved and investigational drugs. 54 approved drugs were selected as candidates, 4 of which were acquired and tested on Cz and T. cruzi epimastigotes. Among them, the antiparkinsonian and antidiabetic drug bromocriptine and the antiarrhythmic amiodarone showed dose-dependent inhibition of Cz and antiproliferative activity on the parasite.
Fil: Bellera, Carolina Leticia. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Química Medicinal; Argentina;
Fil: Balcazar, Dario Emmanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología;
Fil: Alberca, Lucas Nicolás. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Química Medicinal; Argentina;
Fil: Labriola, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires(i); Argentina;
Fil: Talevi, Alan. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Química Medicinal; Argentina;
Fil: Carrillo, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología;
Materia
Chagas Disease
Computer- Aided Drug Repurposing
Cruzipain
Linear Discriminant Analysis
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:11336/1673
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/1673
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effectsBellera, Carolina LeticiaBalcazar, Dario EmmanuelAlberca, Lucas NicolásLabriola, Carlos AlbertoTalevi, AlanCarrillo, CarolinaChagas DiseaseComputer- Aided Drug RepurposingCruzipainLinear Discriminant Analysishttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Cruzipain (Cz) is the major cystein protease of the protozoan Trypanosoma cruzi, etiological agent of Chagas disease. From a 163-compound dataset, a 2D-classifier capable of identifying Cz inhibitors was obtained and applied in a virtual screening campaign on the DrugBank database, which compiles FDA-approved and investigational drugs. 54 approved drugs were selected as candidates, 4 of which were acquired and tested on Cz and T. cruzi epimastigotes. Among them, the antiparkinsonian and antidiabetic drug bromocriptine and the antiarrhythmic amiodarone showed dose-dependent inhibition of Cz and antiproliferative activity on the parasite.Fil: Bellera, Carolina Leticia. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Química Medicinal; Argentina;Fil: Balcazar, Dario Emmanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología;Fil: Alberca, Lucas Nicolás. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Química Medicinal; Argentina;Fil: Labriola, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires(i); Argentina;Fil: Talevi, Alan. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Química Medicinal; Argentina;Fil: Carrillo, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología;American Chemical Society2013-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/1673Bellera, Carolina Leticia; Balcazar, Dario Emmanuel; Alberca, Lucas Nicolás; Labriola, Carlos Alberto; Talevi, Alan; et al.; Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effects; American Chemical Society; Journal of Chemical Information and Modeling; 53; 9; 6-2013; 2402-24081549-9596enginfo:eu-repo/semantics/altIdentifier/doi/DOI:10.1021/ci400284vinfo:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/ci400284vinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:50:21Zoai:ri.conicet.gov.ar:11336/1673instacron: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 09:50:22.286CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effects
title Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effects
spellingShingle Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effects
Bellera, Carolina Leticia
Chagas Disease
Computer- Aided Drug Repurposing
Cruzipain
Linear Discriminant Analysis
title_short Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effects
title_full Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effects
title_fullStr Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effects
title_full_unstemmed Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effects
title_sort Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effects
dc.creator.none.fl_str_mv Bellera, Carolina Leticia
Balcazar, Dario Emmanuel
Alberca, Lucas Nicolás
Labriola, Carlos Alberto
Talevi, Alan
Carrillo, Carolina
author Bellera, Carolina Leticia
author_facet Bellera, Carolina Leticia
Balcazar, Dario Emmanuel
Alberca, Lucas Nicolás
Labriola, Carlos Alberto
Talevi, Alan
Carrillo, Carolina
author_role author
author2 Balcazar, Dario Emmanuel
Alberca, Lucas Nicolás
Labriola, Carlos Alberto
Talevi, Alan
Carrillo, Carolina
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Chagas Disease
Computer- Aided Drug Repurposing
Cruzipain
Linear Discriminant Analysis
topic Chagas Disease
Computer- Aided Drug Repurposing
Cruzipain
Linear Discriminant Analysis
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Cruzipain (Cz) is the major cystein protease of the protozoan Trypanosoma cruzi, etiological agent of Chagas disease. From a 163-compound dataset, a 2D-classifier capable of identifying Cz inhibitors was obtained and applied in a virtual screening campaign on the DrugBank database, which compiles FDA-approved and investigational drugs. 54 approved drugs were selected as candidates, 4 of which were acquired and tested on Cz and T. cruzi epimastigotes. Among them, the antiparkinsonian and antidiabetic drug bromocriptine and the antiarrhythmic amiodarone showed dose-dependent inhibition of Cz and antiproliferative activity on the parasite.
Fil: Bellera, Carolina Leticia. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Química Medicinal; Argentina;
Fil: Balcazar, Dario Emmanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología;
Fil: Alberca, Lucas Nicolás. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Química Medicinal; Argentina;
Fil: Labriola, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires(i); Argentina;
Fil: Talevi, Alan. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Química Medicinal; Argentina;
Fil: Carrillo, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología;
description Cruzipain (Cz) is the major cystein protease of the protozoan Trypanosoma cruzi, etiological agent of Chagas disease. From a 163-compound dataset, a 2D-classifier capable of identifying Cz inhibitors was obtained and applied in a virtual screening campaign on the DrugBank database, which compiles FDA-approved and investigational drugs. 54 approved drugs were selected as candidates, 4 of which were acquired and tested on Cz and T. cruzi epimastigotes. Among them, the antiparkinsonian and antidiabetic drug bromocriptine and the antiarrhythmic amiodarone showed dose-dependent inhibition of Cz and antiproliferative activity on the parasite.
publishDate 2013
dc.date.none.fl_str_mv 2013-06
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/11336/1673
Bellera, Carolina Leticia; Balcazar, Dario Emmanuel; Alberca, Lucas Nicolás; Labriola, Carlos Alberto; Talevi, Alan; et al.; Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effects; American Chemical Society; Journal of Chemical Information and Modeling; 53; 9; 6-2013; 2402-2408
1549-9596
url http://hdl.handle.net/11336/1673
identifier_str_mv Bellera, Carolina Leticia; Balcazar, Dario Emmanuel; Alberca, Lucas Nicolás; Labriola, Carlos Alberto; Talevi, Alan; et al.; Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effects; American Chemical Society; Journal of Chemical Information and Modeling; 53; 9; 6-2013; 2402-2408
1549-9596
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/DOI:10.1021/ci400284v
info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/ci400284v
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
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
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_ 1842269026675326976
score 13.13397

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