Ester-based precursors to increase the bioavailability of quercetin

Plant polyphenols exhibit a variety of potentially useful biochemical properties in vitro, but their evaluation and clinical exploitation in vivo is hampered by their limited bioavailability. Precursors exhibiting resistance to phase II metabolism during absorption are therefore desirable. We report here the synthesis as well as stability and solubility studies of several ester derivatives of quercetin (3,3',4',5,7-pentahydroxy flavone), most of which comprise an aminoacyl group. To model transepithelial absorption, we tested transport across supported tight monolayers of MDCK-1, MDCK-2, and Caco-2 cells. Quercetin itself was extensively conjugated by all three types of cells. A few of our precursors did not cross the monolayers, but others did, undergoing partial deacylation. No phase II conjugation was observed during transport of these compounds across MDCK or some Caco-2 clones. With other Caco-2 lines complete deacylation occurred, followed by metabolism of quercetin. Since elimination of residual acyl groups is expected to take place in vivo, ester derivatives of polyphenols may constitute a useful method to increase systemic aglycone concentrations.