Cytotoxic, Antiangiogenic and Antitelomerase Activity of Glucosyl- and Acyl- Resveratrol Prodrugs and Resveratrol Sulfate Metabolites

Resveratrol (RES) is a natural polyphenol with relevant and varied biological activity. However, its low bioavailability and rapid metabolism to its glucuronate and sulfate conjugates has opened a debate on the mechanisms underlying its bioactivity. RES prodrugs are being developed to overcome these...

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Detalhes bibliográficos
Autores: Falomir, Eva, Lucas Rodríguez, Ricardo, Peñalver, Pablo, Martí Centelles, Rosa, Dupont, Alexia, Zafra-Gómez, Alberto, Carda, Miguel, Morales, Juan C.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Recursos:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/135227
Acesso em linha:https://hdl.handle.net/11441/135227
https://doi.org/10.1002/cbic.201600084
Access Level:acceso abierto
Palavra-chave:Angiogenesis
Antiproliferation
Cytotoxicity
Metabolite
Prodrug
Resveratrol
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spelling Cytotoxic, Antiangiogenic and Antitelomerase Activity of Glucosyl- and Acyl- Resveratrol Prodrugs and Resveratrol Sulfate MetabolitesFalomir, EvaLucas Rodríguez, RicardoPeñalver, PabloMartí Centelles, RosaDupont, AlexiaZafra-Gómez, AlbertoCarda, MiguelMorales, Juan C.AngiogenesisAntiproliferationCytotoxicityMetaboliteProdrugResveratrolResveratrol (RES) is a natural polyphenol with relevant and varied biological activity. However, its low bioavailability and rapid metabolism to its glucuronate and sulfate conjugates has opened a debate on the mechanisms underlying its bioactivity. RES prodrugs are being developed to overcome these problems. We have synthesized a series of RES prodrugs and RES sulfate metabolites (RES-S) and evaluated their biological activities. RES glucosylated prodrugs (RES-Glc) were more cytotoxic in HT-29 and MCF-7 cells than RES itself whereas RES-S showed similar or higher cytotoxicity than RES. VEGF production was decreased by RES-Glc, and RES-disulfate (RES-diS) diminished it even more than RES. Finally, RES-Glc and RES-diS inhibited hTERT gene expression to a higher extent than RES. In conclusion, resveratrol prodrugs are promising candidates as anticancer drugs. In addition, RES-S showed distinct biological activity, thus indicating they are not simply RES reservoirs.Ministerio de Economía y Competitividad CTQ2011–27560, CTQ2012–35360Generalitat Valenciana PROME-TEO/2013/027Universitat Jaume I PI-1B-2011–37Wiley-BlackwellQuímica Orgánica y FarmacéuticaMinisterio de Economía y Competitividad (MINECO). EspañaGeneralitat ValencianaUniversitat Jaume I2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/135227https://doi.org/10.1002/cbic.201600084reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésChemBioChem, 17, 1343-1348.CTQ2011–27560CTQ2012–35360PROME-TEO/2013/027PI-1B-2011–37https://doi.org/10.1002/cbic.201600084info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1352272026-06-17T12:51:07Z
dc.title.none.fl_str_mv Cytotoxic, Antiangiogenic and Antitelomerase Activity of Glucosyl- and Acyl- Resveratrol Prodrugs and Resveratrol Sulfate Metabolites
title Cytotoxic, Antiangiogenic and Antitelomerase Activity of Glucosyl- and Acyl- Resveratrol Prodrugs and Resveratrol Sulfate Metabolites
spellingShingle Cytotoxic, Antiangiogenic and Antitelomerase Activity of Glucosyl- and Acyl- Resveratrol Prodrugs and Resveratrol Sulfate Metabolites
Falomir, Eva
Angiogenesis
Antiproliferation
Cytotoxicity
Metabolite
Prodrug
Resveratrol
title_short Cytotoxic, Antiangiogenic and Antitelomerase Activity of Glucosyl- and Acyl- Resveratrol Prodrugs and Resveratrol Sulfate Metabolites
title_full Cytotoxic, Antiangiogenic and Antitelomerase Activity of Glucosyl- and Acyl- Resveratrol Prodrugs and Resveratrol Sulfate Metabolites
title_fullStr Cytotoxic, Antiangiogenic and Antitelomerase Activity of Glucosyl- and Acyl- Resveratrol Prodrugs and Resveratrol Sulfate Metabolites
title_full_unstemmed Cytotoxic, Antiangiogenic and Antitelomerase Activity of Glucosyl- and Acyl- Resveratrol Prodrugs and Resveratrol Sulfate Metabolites
title_sort Cytotoxic, Antiangiogenic and Antitelomerase Activity of Glucosyl- and Acyl- Resveratrol Prodrugs and Resveratrol Sulfate Metabolites
dc.creator.none.fl_str_mv Falomir, Eva
Lucas Rodríguez, Ricardo
Peñalver, Pablo
Martí Centelles, Rosa
Dupont, Alexia
Zafra-Gómez, Alberto
Carda, Miguel
Morales, Juan C.
author Falomir, Eva
author_facet Falomir, Eva
Lucas Rodríguez, Ricardo
Peñalver, Pablo
Martí Centelles, Rosa
Dupont, Alexia
Zafra-Gómez, Alberto
Carda, Miguel
Morales, Juan C.
author_role author
author2 Lucas Rodríguez, Ricardo
Peñalver, Pablo
Martí Centelles, Rosa
Dupont, Alexia
Zafra-Gómez, Alberto
Carda, Miguel
Morales, Juan C.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Química Orgánica y Farmacéutica
Ministerio de Economía y Competitividad (MINECO). España
Generalitat Valenciana
Universitat Jaume I
dc.subject.none.fl_str_mv Angiogenesis
Antiproliferation
Cytotoxicity
Metabolite
Prodrug
Resveratrol
topic Angiogenesis
Antiproliferation
Cytotoxicity
Metabolite
Prodrug
Resveratrol
description Resveratrol (RES) is a natural polyphenol with relevant and varied biological activity. However, its low bioavailability and rapid metabolism to its glucuronate and sulfate conjugates has opened a debate on the mechanisms underlying its bioactivity. RES prodrugs are being developed to overcome these problems. We have synthesized a series of RES prodrugs and RES sulfate metabolites (RES-S) and evaluated their biological activities. RES glucosylated prodrugs (RES-Glc) were more cytotoxic in HT-29 and MCF-7 cells than RES itself whereas RES-S showed similar or higher cytotoxicity than RES. VEGF production was decreased by RES-Glc, and RES-disulfate (RES-diS) diminished it even more than RES. Finally, RES-Glc and RES-diS inhibited hTERT gene expression to a higher extent than RES. In conclusion, resveratrol prodrugs are promising candidates as anticancer drugs. In addition, RES-S showed distinct biological activity, thus indicating they are not simply RES reservoirs.
publishDate 2016
dc.date.none.fl_str_mv 2016
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 https://hdl.handle.net/11441/135227
https://doi.org/10.1002/cbic.201600084
url https://hdl.handle.net/11441/135227
https://doi.org/10.1002/cbic.201600084
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv ChemBioChem, 17, 1343-1348.
CTQ2011–27560
CTQ2012–35360
PROME-TEO/2013/027
PI-1B-2011–37
https://doi.org/10.1002/cbic.201600084
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley-Blackwell
publisher.none.fl_str_mv Wiley-Blackwell
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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