Cytotoxic, Antiangiogenic and Antitelomerase Activity of Glucosyl- and Acyl- Resveratrol Prodrugs and Resveratrol Sulfate Metabolites.
Por:
Falomir E, Lucas R, Peñalver P, Martí-Centelles R, Dupont A, Zafra-Gómez A, Carda M and Morales JC
Publicada:
15 jul 2016
Resumen:
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.
Filiaciones:
:
Department of Inorganic and Organic Chemistry, University Jaume I, Avda Sos Baynat, sn, 12071, Castellón, Spain
Lucas R:
Department of Bioorganic Chemistry, Instituto de Investigaciones Químicas (IIQ), CSIC-Universidad de Sevilla, Avda Americo Vespucio, 49, 41092, Sevilla, Spain
Peñalver P:
Instituto de Parasitología y Biomedicina "López Neyra", CSIC, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento, 17, 18016, Armilla, Granada, Spain
Martí-Centelles R:
Department of Inorganic and Organic Chemistry, University Jaume I, Avda Sos Baynat, sn, 12071, Castellón, Spain
Dupont A:
Department of Bioorganic Chemistry, Instituto de Investigaciones Químicas (IIQ), CSIC-Universidad de Sevilla, Avda Americo Vespucio, 49, 41092, Sevilla, Spain
Zafra-Gómez A:
Department of Analytical Chemistry, Faculty of Sciences, University of Granada, C/ Severo Ochoa, s/n, 18001, Granada, Spain
Carda M:
Department of Inorganic and Organic Chemistry, University Jaume I, Avda Sos Baynat, sn, 12071, Castellón, Spain.
Morales JC:
Department of Bioorganic Chemistry, Instituto de Investigaciones Químicas (IIQ), CSIC-Universidad de Sevilla, Avda Americo Vespucio, 49, 41092, Sevilla, Spain.
Instituto de Parasitología y Biomedicina "López Neyra", CSIC, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento, 17, 18016, Armilla, Granada, Spain.
|