Labdane conjugates protect cardiomyocytes from doxorubicin-induced cardiotoxicity

The cardiovascular side effects associated with doxorubicin (DOX), a wide spectrum anticancer drug, have limited its clinical application. Therefore, to explore novel strategies with cardioprotective effects, a series of new labdane conjugates were prepared (6a-6c and 8a-8d) from the natural diterpe...

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Detalhes bibliográficos
Autores: Cuadrado, Irene, Oramas-Royo, Sandra, González-Cofrade, Laura, Amesty, Ángel, Hortelano, Sonsoles, Estévez-Braun, Ana, de Las Heras, Beatriz
Tipo de documento: artigo
Data de publicação:2023
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositório:Repisalud
Idioma:inglês
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/16114
Acesso em linha:http://hdl.handle.net/20.500.12105/16114
Access Level:Acceso aberto
Palavra-chave:Myocytes, Cardiac
Diterpenes
Humans
Cardiotoxicity
Signal Transduction
Apoptosis
Doxorubicin
Oxidative Stress
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spelling Labdane conjugates protect cardiomyocytes from doxorubicin-induced cardiotoxicityCuadrado, IreneOramas-Royo, SandraGonzález-Cofrade, LauraAmesty, ÁngelHortelano, SonsolesEstévez-Braun, Anade Las Heras, BeatrizMyocytes, CardiacDiterpenesHumansCardiotoxicitySignal TransductionApoptosisDoxorubicinOxidative StressThe cardiovascular side effects associated with doxorubicin (DOX), a wide spectrum anticancer drug, have limited its clinical application. Therefore, to explore novel strategies with cardioprotective effects, a series of new labdane conjugates were prepared (6a-6c and 8a-8d) from the natural diterpene labdanodiol (1). These hybrid compounds contain anti-inflammatory privileged structures such as naphthalimide, naphthoquinone, and furanonaphthoquinone. Biological activity of these conjugates against DOX-induced cardiotoxicity was tested in vitro and the potential molecular mechanisms of protective effects were explored in H9c2 cardiomyocytes. Three compounds 6c, 8a, and 8b significantly improved cardiomyocyte survival, via inhibition of reactive oxygen species-mediated mitogen-activated protein kinase signaling pathways (extracellular signal-regulated kinase and c-Jun N-terminal kinase) and autophagy mediated by Akt activation. Some structure-activity relationships were outlined, and the best activity was achieved with the labdane-furonaphthoquinone conjugate 8a having an N-cyclohexyl substituent. The findings of this study pave the way for further investigations to obtain more compounds with potential cardioprotective activity.WileyMinisterio de Ciencia, Innovación y Universidades (España)Instituto de Salud Carlos IIIUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Gobierno de Canarias (España)20232023-05-2420232023-02-0120232023-02-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/16114reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/161142026-06-12T12:43:37Z
dc.title.none.fl_str_mv Labdane conjugates protect cardiomyocytes from doxorubicin-induced cardiotoxicity
title Labdane conjugates protect cardiomyocytes from doxorubicin-induced cardiotoxicity
spellingShingle Labdane conjugates protect cardiomyocytes from doxorubicin-induced cardiotoxicity
Cuadrado, Irene
Myocytes, Cardiac
Diterpenes
Humans
Cardiotoxicity
Signal Transduction
Apoptosis
Doxorubicin
Oxidative Stress
title_short Labdane conjugates protect cardiomyocytes from doxorubicin-induced cardiotoxicity
title_full Labdane conjugates protect cardiomyocytes from doxorubicin-induced cardiotoxicity
title_fullStr Labdane conjugates protect cardiomyocytes from doxorubicin-induced cardiotoxicity
title_full_unstemmed Labdane conjugates protect cardiomyocytes from doxorubicin-induced cardiotoxicity
title_sort Labdane conjugates protect cardiomyocytes from doxorubicin-induced cardiotoxicity
dc.creator.none.fl_str_mv Cuadrado, Irene
Oramas-Royo, Sandra
González-Cofrade, Laura
Amesty, Ángel
Hortelano, Sonsoles
Estévez-Braun, Ana
de Las Heras, Beatriz
author Cuadrado, Irene
author_facet Cuadrado, Irene
Oramas-Royo, Sandra
González-Cofrade, Laura
Amesty, Ángel
Hortelano, Sonsoles
Estévez-Braun, Ana
de Las Heras, Beatriz
author_role author
author2 Oramas-Royo, Sandra
González-Cofrade, Laura
Amesty, Ángel
Hortelano, Sonsoles
Estévez-Braun, Ana
de Las Heras, Beatriz
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Instituto de Salud Carlos III
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Gobierno de Canarias (España)
dc.subject.none.fl_str_mv Myocytes, Cardiac
Diterpenes
Humans
Cardiotoxicity
Signal Transduction
Apoptosis
Doxorubicin
Oxidative Stress
topic Myocytes, Cardiac
Diterpenes
Humans
Cardiotoxicity
Signal Transduction
Apoptosis
Doxorubicin
Oxidative Stress
description The cardiovascular side effects associated with doxorubicin (DOX), a wide spectrum anticancer drug, have limited its clinical application. Therefore, to explore novel strategies with cardioprotective effects, a series of new labdane conjugates were prepared (6a-6c and 8a-8d) from the natural diterpene labdanodiol (1). These hybrid compounds contain anti-inflammatory privileged structures such as naphthalimide, naphthoquinone, and furanonaphthoquinone. Biological activity of these conjugates against DOX-induced cardiotoxicity was tested in vitro and the potential molecular mechanisms of protective effects were explored in H9c2 cardiomyocytes. Three compounds 6c, 8a, and 8b significantly improved cardiomyocyte survival, via inhibition of reactive oxygen species-mediated mitogen-activated protein kinase signaling pathways (extracellular signal-regulated kinase and c-Jun N-terminal kinase) and autophagy mediated by Akt activation. Some structure-activity relationships were outlined, and the best activity was achieved with the labdane-furonaphthoquinone conjugate 8a having an N-cyclohexyl substituent. The findings of this study pave the way for further investigations to obtain more compounds with potential cardioprotective activity.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-05-24
2023
2023-02-01
2023
2023-02-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/16114
url http://hdl.handle.net/20.500.12105/16114
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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