On the discovery of a potential survivin inhibitor combining computational tools and cytotoxicity studies

Autores
Quispe Castillo, Patricia Araceli; Lavecchia, Martín José; Leon, Ignacio Esteban
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Survivin protein is a metalloprotein member of the inhibitors of apoptosis proteins family, involved in the regulation of programmed cell death. Due to the recent development of antitumor therapies having survivin as molecular target, several strategies to interfere with the expression or function of survivin have emerged. This work describes the discovery of a new potential inhibitor of survivin function using a computer-aided drug design approach. Structure-based virtual screening and molecular dynamic simulations were carried out to select two compounds as possible inhibitors. According to the binding energy, possible ligand localization is in a cavity, close to dimerization interface. Next, cell-based assays were performed on three cell lines: two with tumor phenotype and over-expression of survivin, and another with normal phenotype and low expression of survivin. One of the selected compounds shows a selectively antitumor effect on panel cell lines suggesting that the compound effect could be correlated with the survivin expression.
Fil: Quispe Castillo, Patricia Araceli. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Lavecchia, Martín José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Leon, Ignacio Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Materia
BIOINFORMATICS
COMPUTATIONAL BIOLOGY
DOCKING STUDIES
INHIBITORS
MOLECULAR BIOLOGY
MOLECULAR DYNAMICS
SURVIVIN
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:11336/124847
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/124847
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling On the discovery of a potential survivin inhibitor combining computational tools and cytotoxicity studiesQuispe Castillo, Patricia AraceliLavecchia, Martín JoséLeon, Ignacio EstebanBIOINFORMATICSCOMPUTATIONAL BIOLOGYDOCKING STUDIESINHIBITORSMOLECULAR BIOLOGYMOLECULAR DYNAMICSSURVIVINhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Survivin protein is a metalloprotein member of the inhibitors of apoptosis proteins family, involved in the regulation of programmed cell death. Due to the recent development of antitumor therapies having survivin as molecular target, several strategies to interfere with the expression or function of survivin have emerged. This work describes the discovery of a new potential inhibitor of survivin function using a computer-aided drug design approach. Structure-based virtual screening and molecular dynamic simulations were carried out to select two compounds as possible inhibitors. According to the binding energy, possible ligand localization is in a cavity, close to dimerization interface. Next, cell-based assays were performed on three cell lines: two with tumor phenotype and over-expression of survivin, and another with normal phenotype and low expression of survivin. One of the selected compounds shows a selectively antitumor effect on panel cell lines suggesting that the compound effect could be correlated with the survivin expression.Fil: Quispe Castillo, Patricia Araceli. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Lavecchia, Martín José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Leon, Ignacio Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaElsevier2019-08-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/124847Quispe Castillo, Patricia Araceli; Lavecchia, Martín José; Leon, Ignacio Esteban; On the discovery of a potential survivin inhibitor combining computational tools and cytotoxicity studies; Elsevier; Heliyon; 5; 8; 1-8-2019; 1-92405-8440CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S2405844019358980info:eu-repo/semantics/altIdentifier/doi/10.1016/j.heliyon.2019.e02238info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:25:08Zoai:ri.conicet.gov.ar:11336/124847instacron: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:34982025-10-22 11:25:08.395CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv On the discovery of a potential survivin inhibitor combining computational tools and cytotoxicity studies
title On the discovery of a potential survivin inhibitor combining computational tools and cytotoxicity studies
spellingShingle On the discovery of a potential survivin inhibitor combining computational tools and cytotoxicity studies
Quispe Castillo, Patricia Araceli
BIOINFORMATICS
COMPUTATIONAL BIOLOGY
DOCKING STUDIES
INHIBITORS
MOLECULAR BIOLOGY
MOLECULAR DYNAMICS
SURVIVIN
title_short On the discovery of a potential survivin inhibitor combining computational tools and cytotoxicity studies
title_full On the discovery of a potential survivin inhibitor combining computational tools and cytotoxicity studies
title_fullStr On the discovery of a potential survivin inhibitor combining computational tools and cytotoxicity studies
title_full_unstemmed On the discovery of a potential survivin inhibitor combining computational tools and cytotoxicity studies
title_sort On the discovery of a potential survivin inhibitor combining computational tools and cytotoxicity studies
dc.creator.none.fl_str_mv Quispe Castillo, Patricia Araceli
Lavecchia, Martín José
Leon, Ignacio Esteban
author Quispe Castillo, Patricia Araceli
author_facet Quispe Castillo, Patricia Araceli
Lavecchia, Martín José
Leon, Ignacio Esteban
author_role author
author2 Lavecchia, Martín José
Leon, Ignacio Esteban
author2_role author
author
dc.subject.none.fl_str_mv BIOINFORMATICS
COMPUTATIONAL BIOLOGY
DOCKING STUDIES
INHIBITORS
MOLECULAR BIOLOGY
MOLECULAR DYNAMICS
SURVIVIN
topic BIOINFORMATICS
COMPUTATIONAL BIOLOGY
DOCKING STUDIES
INHIBITORS
MOLECULAR BIOLOGY
MOLECULAR DYNAMICS
SURVIVIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Survivin protein is a metalloprotein member of the inhibitors of apoptosis proteins family, involved in the regulation of programmed cell death. Due to the recent development of antitumor therapies having survivin as molecular target, several strategies to interfere with the expression or function of survivin have emerged. This work describes the discovery of a new potential inhibitor of survivin function using a computer-aided drug design approach. Structure-based virtual screening and molecular dynamic simulations were carried out to select two compounds as possible inhibitors. According to the binding energy, possible ligand localization is in a cavity, close to dimerization interface. Next, cell-based assays were performed on three cell lines: two with tumor phenotype and over-expression of survivin, and another with normal phenotype and low expression of survivin. One of the selected compounds shows a selectively antitumor effect on panel cell lines suggesting that the compound effect could be correlated with the survivin expression.
Fil: Quispe Castillo, Patricia Araceli. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Lavecchia, Martín José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Leon, Ignacio Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
description Survivin protein is a metalloprotein member of the inhibitors of apoptosis proteins family, involved in the regulation of programmed cell death. Due to the recent development of antitumor therapies having survivin as molecular target, several strategies to interfere with the expression or function of survivin have emerged. This work describes the discovery of a new potential inhibitor of survivin function using a computer-aided drug design approach. Structure-based virtual screening and molecular dynamic simulations were carried out to select two compounds as possible inhibitors. According to the binding energy, possible ligand localization is in a cavity, close to dimerization interface. Next, cell-based assays were performed on three cell lines: two with tumor phenotype and over-expression of survivin, and another with normal phenotype and low expression of survivin. One of the selected compounds shows a selectively antitumor effect on panel cell lines suggesting that the compound effect could be correlated with the survivin expression.
publishDate 2019
dc.date.none.fl_str_mv 2019-08-01
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/11336/124847
Quispe Castillo, Patricia Araceli; Lavecchia, Martín José; Leon, Ignacio Esteban; On the discovery of a potential survivin inhibitor combining computational tools and cytotoxicity studies; Elsevier; Heliyon; 5; 8; 1-8-2019; 1-9
2405-8440
CONICET Digital
CONICET
url http://hdl.handle.net/11336/124847
identifier_str_mv Quispe Castillo, Patricia Araceli; Lavecchia, Martín José; Leon, Ignacio Esteban; On the discovery of a potential survivin inhibitor combining computational tools and cytotoxicity studies; Elsevier; Heliyon; 5; 8; 1-8-2019; 1-9
2405-8440
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://linkinghub.elsevier.com/retrieve/pii/S2405844019358980
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.heliyon.2019.e02238
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 Elsevier
publisher.none.fl_str_mv Elsevier
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 12.982451

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