Cytotoxic, Antiangiogenic and Antitelomerase Activity of Glucosyl‐ and Acyl‐ Resveratrol Prodrugs and Resveratrol Sulfate Metabolites. (20th June 2016)

• Record Type: Journal Article
• Authors: Falomir, Eva; Lucas, Ricardo; Peñalver, Pablo; Martí‐Centelles, Rosa; Dupont, Alexia; Zafra‐Gómez, Alberto; Carda, Miguel; Morales, Juan C.
• Is Part Of: Chembiochem. Volume 17:Number 14(2016)
• Page Start: 1343
• Page End: 1348
• Publication Date: 2016-06-20
• Subjects: angiogenesis -- antiproliferation -- cytotoxicity -- metabolite -- prodrug -- resveratrol; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201600084
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: 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. Abstract : Improved resveratrol activity : Glucosylated resveratrol prodrugs and resveratrol sulfate metabolites show improved anti‐proliferative and anti‐angiogenic activity in comparison to resveratrol itself. These results suggest resveratrol derivatives as potential drugs and confirm that resveratrol sulfate metabolites contribute to the in vivo biological activity observed for the parent compound.