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

AutorFalomir, Eva; Lucas, Ricardo ; Peñalver, Pablo ; Martí-Centelles, Rosa; Dupont, Alexia; Zafra-Gómez, Alberto; Carda, Miguel; Morales, Juan C.
Palabras claveAngiogenesis
Antiproliferation
Cytotoxicity
Metabolite
Prodrug
resveratrol
Fecha de publicación4-may-2016
EditorJohn Wiley & Sons
CitaciónChemBioChem
ResumenResveratrol (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.
Versión del editorhttps://onlinelibrary.wiley.com/doi/full/10.1002/cbic.201600084#support-information-section
URIhttp://hdl.handle.net/10261/163600
DOI10.1002/cbic.201600084
ISSN1439-4227
E-ISSN1439-7633
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