The Influence of Glycosylation of Natural and Synthetic Prenylated Flavonoids on Binding to Human Serum Albumin and Inhibition of Cyclooxygenases COX-1 and COX-2

Abstract

The synthesis of different classes of prenylated aglycones (α,β-dihydroxanthohumol (<b>2</b>) and (<i>Z</i>)-6,4'-dihydroxy-4-methoxy-7-prenylaurone (<b>3</b>)) was performed in one step reactions from xanthohumol (<b>1</b>)-major prenylated chalcone naturally occurring in hops. Obtained flavonoids (<b>2</b>-<b>3</b>) and xanthohumol (<b>1</b>) were used as substrates for regioselective fungal glycosylation catalyzed by two <i>Absidia</i> species and <i>Beauveria bassiana</i>. As a result six glycosides (<b>4</b>-<b>9</b>) were formed, of which four glycosides (<b>6</b>-<b>9</b>) have not been published so far. The influence of flavonoid skeleton and the presence of glucopyranose and 4-<i>O</i>-methylglucopyranose moiety in flavonoid molecule on binding to main protein in plasma, human serum albumin (HSA), and inhibition of cyclooxygenases COX-1 and COX-2 were investigated. Results showed that chalcone (<b>1</b>) had the highest binding affinity to HSA (8.624 × 10⁴ M^-1) of all tested compounds. It has also exhibited the highest inhibition of cyclooxygenases activity, and it was a two-fold stronger inhibitor than α,β-dihydrochalcone (<b>2</b>) and aurone (<b>3</b>). The presence of sugar moiety in flavonoid molecule caused the loss of HSA binding activity as well as the decrease in inhibition of cyclooxygenases activity.