676596-85-3

Upstream product

• 120743-99-9 p-[(tert-butyldimethylsilyl)oxy]benzaldehyde 
• 103929-84-6 [3,5-di(tert-butyldimethylsilanyloxy)phenyl]methanol 
• 103929-85-7 3,5-bis(tert-butyldimethylsilyloxy)benzyl chloride 
• 501-36-0 (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol 
• 18162-48-6 tert-butyldimethylsilyl chloride 
• 69739-34-0 t-butyldimethylsiyl triflate 
• 158139-69-6 5-(bromomethyl)-1,3-bis(tert-butyldimethylsilyloxy)-benzene 
• 99-10-5 3,5-Dihydroxybenzoic acid 
• 103929-83-5 methyl 3,5-bis(tert-butyldimethylsilyloxy)benzoate 
• 123-08-0 4-hydroxy-benzaldehyde 
• 2150-44-9 1-carbomethoxy-3,5-dihydroxybenzene 
• 869011-52-9 diethyl [3,5-bis(tert-butyldimethylsilyloxy)phenyl]methylphosphonate 

Downstream Products

• 501-36-0 (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol 

Relevant academic research and scientific papers

Silyl resveratrol derivatives as potential therapeutic agents for neurodegenerative and neurological diseases

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.

SILYLATED DERIVATIVES OF RESERVATROL AND THE USE THEREOF IN NEURODEGENERATIVE, NEUROLOGICAL OR INFLAMMATORY DISEASES

The present invention relates to a group of compounds derived from resveratrol having as substituents at least one silyl group which, in turn, can be substituted by different groups. The invention also relates to the therapeutic use of these compounds in inflammatory, neurological, and neurodegenerative diseases.

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

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.

Preventive oral treatment with resveratrol pro-prodrugs drastically reduce colon inflammation in rodents

There is no pharmaceutical or definitive surgical cure for inflammatory bowel diseases (IBDs). The naturally occurring polyphenol resveratrol exerts anti-inflammatory properties. However, its rapid metabolism diminishes its effectiveness in the colon. The design of prodrugs to targeting active molecules to the colon provides an opportunity for therapy of IBDs. Herein we explore the efficacy of different resveratrol prodrugs and pro-prodrugs to ameliorate colon inflammation in the murine dextran sulfate sodium (DSS) model. Mice fed with a very low dose (equivalent to 10 mg for a 70 kg-person) of either resveratrol-3-O-(6′-O-butanoyl)-β-d-glucopyranoside (6) or resveratrol-3-O-(6′-O-octanoyl)-β-d-glucopyranoside (7) did not develop colitis symptoms and improved 6-fold the disease activity index (DAI) compared to resveratrol. Our results indicate that these pro-prodrugs exerted a dual effect: (1) they prevented the rapid metabolism of resveratrol and delivered higher quantities of resveratrol to the colon and (2) they reduced mucosal barrier imbalance and prevented diarrhea, which consequently facilitated the action of the delivered resveratrol in the colon mucosa.

Biomimic transformation of resveratrol

Resveratrol was treated with several kinds of peroxidases and inorganic reagents so as to prepare ε-viniferin. Among several inorganic reagents, which were investigated in this study, thallium(III) nitrate in methanol gave (±)-ε-viniferin in the yield of 68%. On the other hand, peroxidases did not lead to ε-viniferin, but some stilbenedimers such as pallidol, resveratrol trans-dehydrodimer, and leachianol F were obtained.

Syntheses and radical scavenging activities of resveratrol derivatives

Nine new resveratrol derivatives, having bromo, iodo, and fluoroethyl groups, were designed and synthesized. All compounds having free phenol groups showed good free radical scavenging activity. Among them, 2-bromoresveratrol 19 has a similar free radical scavenging activity to (+)-catechin.