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

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, differen...

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Autores: Hernández, Ángela-Patricia, Díez, Paula, García, Pablo A., Pérez-Andrés, Martín, Ortega, Pablo, Jambrina, Pablo G., Díez, David, Castro, María Ángeles, Fuentes, Manuel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/166972
Acceso en línea:http://hdl.handle.net/10366/166972
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, MartínOrtega, PabloJambrina, Pablo G.Díez, DavidCastro, María ÁngelesFuentes, Manuelpodophyllotoxinetoposideprotein inhibitiontubulin polymerizationanti-topoisomerase-IIhybridizationconjugationcytotoxicityflow cytometrymolecular dockingNatural 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.202520252020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10366/166972reponame:GREDOS. Repositorio Institucional de la Universidad de Salamancainstname:Universidad de Salamanca (USAL)InglésAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:gredos.usal.es:10366/1669722026-06-07T06:28:51Z
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, Martín
Ortega, Pablo
Jambrina, Pablo G.
Díez, David
Castro, María Ángeles
Fuentes, Manuel
author Hernández, Ángela-Patricia
author_facet Hernández, Ángela-Patricia
Díez, Paula
García, Pablo A.
Pérez-Andrés, Martín
Ortega, Pablo
Jambrina, Pablo G.
Díez, David
Castro, María Ángeles
Fuentes, Manuel
author_role author
author2 Díez, Paula
García, Pablo A.
Pérez-Andrés, Martín
Ortega, Pablo
Jambrina, Pablo G.
Díez, David
Castro, María Ángeles
Fuentes, Manuel
author2_role author
author
author
author
author
author
author
author
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 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.
publishDate 2020
dc.date.none.fl_str_mv 2020
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10366/166972
url http://hdl.handle.net/10366/166972
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:GREDOS. Repositorio Institucional de la Universidad de Salamanca
instname:Universidad de Salamanca (USAL)
instname_str Universidad de Salamanca (USAL)
reponame_str GREDOS. Repositorio Institucional de la Universidad de Salamanca
collection GREDOS. Repositorio Institucional de la Universidad de Salamanca
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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