N-Monosubstituted Methoxy-oligoethylene glycol Carbamate Ester Prodrugs of ResveratrolReport as inadecuate




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1

Department of Chemical Sciences, University of Padova, Via F. Marzolo, Padova 135131, Italy

2

Department of Biomedical Sciences, University of Padova, Viale G. Colombo, Padova 335121, Italy

3

CNR Neuroscience Institute, Viale G. Colombo, Padova 335121, Italy

4

OS srl, Via Campello sul Clitunno, Roma 3400181, Italy



These authors contributed equally to this work.





*

Author to whom correspondence should be addressed.



Academic Editors: Emilie Combet and Maria Rosário Bronze

Abstract Resveratrol is a natural polyphenol with many interesting biological activities. Its pharmacological exploitation in vivo is, however, hindered by its rapid elimination via phase II conjugative metabolism at the intestinal and, most importantly, hepatic levels. One approach to bypass this problem relies on prodrugs. We report here the synthesis, characterization, hydrolysis, and in vivo pharmacokinetic behavior of resveratrol prodrugs in which the OH groups are engaged in an N-monosubstituted carbamate ester linkage. As promoiety, methoxy-oligoethylene glycol groups m-OEG CH3–OCH2CH2n– of defined chain length n = 3, 4, 6 were used. These are expected to modulate the chemico-physical properties of the resulting derivatives, much like longer polyethylene glycol PEG chains, while retaining a relatively low MW and, thus, a favorable drug loading capacity. Intragastric administration to rats resulted in the appearance in the bloodstream of the prodrug and of the products of its partial hydrolysis, confirming protection from first-pass metabolism during absorption. View Full-Text

Keywords: resveratrol; prodrugs; methoxy-oligoethylene glycol; polyethylene glycol; polyphenols; bioavailability; carbamate ester resveratrol; prodrugs; methoxy-oligoethylene glycol; polyethylene glycol; polyphenols; bioavailability; carbamate ester





Author: Andrea Mattarei 1,†,* , Michele Azzolini 2,3,4,†, Mario Zoratti 2,3, Lucia Biasutto 2,3 and Cristina Paradisi 1

Source: http://mdpi.com/



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