Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/16114
Título
Labdane conjugates protect cardiomyocytes from doxorubicin-induced cardiotoxicity
Autor(es)
Fecha de publicación
2023-02
Cita
Drug Dev Res. 2023 Feb;84(1):84-95.
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
Palabras clave
MESH
Myocytes, Cardiac | Diterpenes | Humans | Cardiotoxicity | Signal Transduction | Apoptosis | Doxorubicin | Oxidative Stress
Versión en línea
DOI
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