New Water-Soluble Carbamate Ester Derivatives of Resveratrol

Molecules

Andrea Mattarei³  Massimo Carraro²  Michele Azzolini¹  Cristina Paradisi³  Mario Zoratti¹  Lucia Biasutto¹ 

[1] Department of Biomedical Sciences, University of Padova, Viale G. Colombo 3, 35121 Padova, Italy; E-Mails:;Department of Chemistry and Pharmacy, University of Sassari, Viale Vienna 2, 07100 Sassari, Italy; E-Mail:;Department of Chemical Sciences, University of Padova, Via F. Marzolo 1, 35131 Padova, Italy; E-Mails:

关键词: resveratrol;    prodrugs;    carbamate esters;    solubility;    poly(ethylene glycol);    glucose;   

DOI  :  10.3390/molecules191015900

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.