New Water-Soluble Carbamate Ester Derivatives of Resveratrol
| Autor: | Cristina Paradisi, Michele Azzolini, Mario Zoratti, Massimo Carraro, Lucia Biasutto, Andrea Mattarei |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Carbamate medicine.medical_treatment Pharmaceutical Science resveratrol Resveratrol Article Permeability Analytical Chemistry lcsh:QD241-441 chemistry.chemical_compound Hydrolysis lcsh:Organic chemistry prodrugs Oral administration Stilbenes Drug Discovery medicine Animals Organic chemistry Intestinal Mucosa glucose Physical and Theoretical Chemistry Solubility Molecular Structure poly(ethylene glycol) Chemistry solubility Organic Chemistry carbamate esters Water Esters Prodrug Rats Bioavailability CHIM/06 Chimica organica Chemistry (miscellaneous) Molecular Medicine Carbamates Ethylene glycol |
| Zdroj: | Molecules Volume 19 Issue 10 Pages 15900-15917 Molecules, Vol 19, Iss 10, Pp 15900-15917 (2014) |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules191015900 |
| Popis: | Low bioavailability severely hinders exploitation of the biomedical potential of resveratrol. Extensive phase-II metabolism and poor water solubility contribute to lowering the concentrations of resveratrol in the bloodstream after oral administration. Prodrugs may provide a solution—protection of the phenolic functions hinders conjugative metabolism and can be exploited to modulate the physicochemical properties of the compound. We report here the synthesis and characterization of carbamate ester derivatives of resveratrol bearing on each nitrogen atom a methyl group and either a methoxy-poly(ethylene glycol)-350 (mPEG-350) or a butyl-glucosyl promoiety conferring high water solubility. Ex vivo absorption studies revealed that the butyl-glucosyl conjugate, unlike the mPEG-350 one, is able to permeate the intestinal wall. In vivo pharmacokinetics confirmed absorption after oral administration and showed that no hydrolysis of the carbamate groups takes place. Thus, sugar groups can be attached to resveratrol to obtain soluble derivatives maintaining to some degree the ability to permeate biomembranes, perhaps by facilitated or active transport. |
| Databáze: | OpenAIRE |
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