title: Cytotoxic, Antiangiogenic and Antitelomerase Activity of Glucosyl- and Acyl- Resveratrol Prodrugs and Resveratrol Sulfate Metabolites.
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.
authors.affiliation: Department of Inorganic and Organic Chemistry, University Jaume I, Avda Sos Baynat, sn, 12071, Castellón, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Falomir
authors.affiliation: Department of Bioorganic Chemistry, Instituto de Investigaciones Químicas (IIQ), CSIC-Universidad de Sevilla, Avda Americo Vespucio, 49, 41092, Sevilla, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Lucas
authors.affiliation: Instituto de Parasitología y Biomedicina "López Neyra", CSIC, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento, 17, 18016, Armilla, Granada, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Peñalver
authors.affiliation: Department of Inorganic and Organic Chemistry, University Jaume I, Avda Sos Baynat, sn, 12071, Castellón, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Martí-Centelles
authors.affiliation: Department of Bioorganic Chemistry, Instituto de Investigaciones Químicas (IIQ), CSIC-Universidad de Sevilla, Avda Americo Vespucio, 49, 41092, Sevilla, Spain.
authors.forename: Alexia
authors.initials: A
authors.lastname: Dupont
authors.affiliation: Department of Analytical Chemistry, Faculty of Sciences, University of Granada, C/ Severo Ochoa, s/n, 18001, Granada, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Zafra-Gómez
authors.affiliation: Department of Inorganic and Organic Chemistry, University Jaume I, Avda Sos Baynat, sn, 12071, Castellón, Spain. mcarda@qio.uji.es.
authors.forename: Miguel
authors.initials: M
authors.lastname: Carda
authors.affiliation: Department of Bioorganic Chemistry, Instituto de Investigaciones Químicas (IIQ), CSIC-Universidad de Sevilla, Avda Americo Vespucio, 49, 41092, Sevilla, Spain. jcmorales@ipb.csic.es.|Instituto de Parasitología y Biomedicina "López Neyra", CSIC, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento, 17, 18016, Armilla, Granada, Spain. jcmorales@ipb.csic.es.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Morales
mesh_terms: D000215:Acylation; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D006031:Glycosylation; D019073:HT29 Cells; D006801:Humans; D061986:MCF-7 Cells; D011355:Prodrugs / Q000737:chemistry* / Q000493:pharmacokinetics; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D013431:Sulfates / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D011355:Prodrugs; D013267:Stilbenes; D013431:Sulfates; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C509186:TERT protein, human; D019098:Telomerase; D000077185:Resveratrol
keywords: angiogenesis; antiproliferation; cytotoxicity; metabolite; prodrug; resveratrol