RT Journal Article
T1 Silyl resveratrol derivatives as potential therapeutic agents for neurodegenerative and neurological diseases.
A1 Belmonte-Reche, Efres
A1 Peñalver, Pablo
A1 Caro-Moreno, Marta
A1 Mateos-Martín, María Luisa
A1 Adán, Norma
A1 Delgado, Mario
A1 González-Rey, Elena
A1 Morales, Juan Carlos
K1 Huntington disease
K1 Multiple sclerosis
K1 Neurodegenerative diseases
K1 Prodrug
K1 Resveratrol
K1 Silyl group
AB Natural phenolic compounds found in food have demonstrated interesting preventive and therapeutic effects on a large variety of pathologies. Indeed, some of them, such as resveratrol (RES), have been examined in clinical trials. Nevertheless, their success has been scarce mainly due to their low bioavailability. In this study, we found serendipitously that O-silyl RES derivatives exerted a better neuroprotective activity than resveratrol itself and decided to explore them as potential drugs for neurodegenerative and neurological diseases. We have also designed and prepared a series of O-silyl RES prodrugs to improve their bioavailability. We found that di-triethylsilyl and di-triisopropylsilyl RES derivatives were better in vitro neuroprotective and anti-inflammatory agents than RES. Among these derivatives and their corresponding acyl-, glycosyl- and carbamoyl-prodrugs, 3,5-triethylsilyl-4'-(6″-octanoylglucopyranosyl) resveratrol 26 showed the best profile on toxicity and neuroprotective activity in zebra fish embryo. Compound 26 was also capable of reducing the loss of motor coordination in a 3-nitropropionic acid mice model of Huntington's disease, in a similar way to RES. However, 26 diminished pro-inflammatory cytokine IL-6 to a higher extent than RES and improved the latency to fall in the rotarod test by 10% with respect to RES. Finally, we investigated 26 and RES as potential treatments on an experimental autoimmune encephalomyelitis (EAE) multiple sclerosis mice model. We observed that, in a therapeutic regimen, 26 significantly diminished the progression of EAE severity and reduced the percentage of animals with moderate to severe clinical score, whereas RES showed no improvement.
YR 2021
FD 2021-06-18
LK https://hdl.handle.net/10668/27499
UL https://hdl.handle.net/10668/27499
LA en
DS RISalud
RD Apr 12, 2025