A Novel Cytotoxic Conjugate Derived from the Natural Product Podophyllotoxin as a Direct-Target Protein Dual Inhibitor

© 2020 by the authors.

Detalles Bibliográficos
Autores: Hernández, Ángela-Patricia, Díez, Paula, García, Pablo A., Pérez-Andrés, Martin, Ortega, Pablo, Jambrina, Pablo G., Díez, David, Castro, M. Ángeles, Fuentes, Manuel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/226453
Acceso en línea:http://hdl.handle.net/10261/226453
Access Level:acceso abierto
Palabra clave:Podophyllotoxin
Etoposide
Protein inhibition
Tubulin polymerization
Anti-topoisomerase-II
Hybridization
Conjugation
Cytotoxicity
Flow cytometry
Molecular docking
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spelling A Novel Cytotoxic Conjugate Derived from the Natural Product Podophyllotoxin as a Direct-Target Protein Dual InhibitorHernández, Ángela-PatriciaDíez, PaulaGarcía, Pablo A.Pérez-Andrés, MartinOrtega, PabloJambrina, Pablo G.Díez, DavidCastro, M. ÁngelesFuentes, ManuelPodophyllotoxinEtoposideProtein inhibitionTubulin polymerizationAnti-topoisomerase-IIHybridizationConjugationCytotoxicityFlow cytometryMolecular docking© 2020 by the authors.Natural products are the ideal basis for the design of novel efficient molecular entities. Podophyllotoxin, a naturally occurring cyclolignan, is an example of natural product which displays a high versatility from a biological activity point of view. Based on its unique chemical structure, different derivatives have been synthesized presenting the original antitumoral properties associated with the compound, i.e., the tubulin polymerization inhibition and arising anti-topoisomerase II activity from structural modifications on the cyclolignan skeleton. In this report, we present a novel conjugate or hybrid which chemically combines both biological activities in one single molecule. Chemical design has been planned based in our lead compound, podophyllic aldehyde, as an inhibitor of tubulin polymerization, and in etoposide, an approved antitumoral drug targeting topoisomerase II. The cytotoxicity and selectivity of the novel synthetized hybrid has been evaluated in several cell lines of different solid tumors. In addition, these dual functional effects of the novel compound have been also evaluated by molecular docking approaches.Financial support came from Spanish MINECO (CTQ2015-68175-R, AGL2016-79813-C2-2-R), Junta de Castilla y León (BIO/SA07/15), ISCIII-RICET Network (RD16/0027/0018) cofinanced by the Fondo Social Europeo of the European Union (Fondos FEDER–EU) and USAL (Financiación GIR). Fundación Solórzano (FS/23-2015) has also sponsored this work. The Proteomics Unit belongs to ProteoRed, PRB2-ISCIII, supported by Grant No. PT13/0001, of the PE I+D+I 2013–2016, funded by ISCIII and FEDER.Molecular Diversity Preservation InternationalMinisterio de Economía y Competitividad (España)Junta de Castilla y LeónInstituto de Salud Carlos IIIEuropean CommissionUniversidad de SalamancaFundación Memoria de D. Samuel Solorzano BarrusoConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120202021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/226453reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2015-68175-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/AGL2016-79813-C2-2-Rhttp://dx.doi.org/10.3390/molecules25184258Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2264532026-05-22T06:33:51Z
dc.title.none.fl_str_mv A Novel Cytotoxic Conjugate Derived from the Natural Product Podophyllotoxin as a Direct-Target Protein Dual Inhibitor
title A Novel Cytotoxic Conjugate Derived from the Natural Product Podophyllotoxin as a Direct-Target Protein Dual Inhibitor
spellingShingle A Novel Cytotoxic Conjugate Derived from the Natural Product Podophyllotoxin as a Direct-Target Protein Dual Inhibitor
Hernández, Ángela-Patricia
Podophyllotoxin
Etoposide
Protein inhibition
Tubulin polymerization
Anti-topoisomerase-II
Hybridization
Conjugation
Cytotoxicity
Flow cytometry
Molecular docking
title_short A Novel Cytotoxic Conjugate Derived from the Natural Product Podophyllotoxin as a Direct-Target Protein Dual Inhibitor
title_full A Novel Cytotoxic Conjugate Derived from the Natural Product Podophyllotoxin as a Direct-Target Protein Dual Inhibitor
title_fullStr A Novel Cytotoxic Conjugate Derived from the Natural Product Podophyllotoxin as a Direct-Target Protein Dual Inhibitor
title_full_unstemmed A Novel Cytotoxic Conjugate Derived from the Natural Product Podophyllotoxin as a Direct-Target Protein Dual Inhibitor
title_sort A Novel Cytotoxic Conjugate Derived from the Natural Product Podophyllotoxin as a Direct-Target Protein Dual Inhibitor
dc.creator.none.fl_str_mv Hernández, Ángela-Patricia
Díez, Paula
García, Pablo A.
Pérez-Andrés, Martin
Ortega, Pablo
Jambrina, Pablo G.
Díez, David
Castro, M. Ángeles
Fuentes, Manuel
author Hernández, Ángela-Patricia
author_facet Hernández, Ángela-Patricia
Díez, Paula
García, Pablo A.
Pérez-Andrés, Martin
Ortega, Pablo
Jambrina, Pablo G.
Díez, David
Castro, M. Ángeles
Fuentes, Manuel
author_role author
author2 Díez, Paula
García, Pablo A.
Pérez-Andrés, Martin
Ortega, Pablo
Jambrina, Pablo G.
Díez, David
Castro, M. Ángeles
Fuentes, Manuel
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Junta de Castilla y León
Instituto de Salud Carlos III
European Commission
Universidad de Salamanca
Fundación Memoria de D. Samuel Solorzano Barruso
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Podophyllotoxin
Etoposide
Protein inhibition
Tubulin polymerization
Anti-topoisomerase-II
Hybridization
Conjugation
Cytotoxicity
Flow cytometry
Molecular docking
topic Podophyllotoxin
Etoposide
Protein inhibition
Tubulin polymerization
Anti-topoisomerase-II
Hybridization
Conjugation
Cytotoxicity
Flow cytometry
Molecular docking
description © 2020 by the authors.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/226453
url http://hdl.handle.net/10261/226453
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2015-68175-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/AGL2016-79813-C2-2-R
http://dx.doi.org/10.3390/molecules25184258
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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