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.

The synthesis of different classes of prenylated aglycones (α,β-dihydroxanthohumol ( 2 ) and ( Z )-6,4'-dihydroxy-4-methoxy-7-prenylaurone ( 3 )) was performed in one step reactions from xanthohumol ( 1 )-major prenylated chalcone naturally occurring in hops. Obtained flavonoids ( 2 - 3 ) and xanthohumol ( 1 ) were used as substrates for regioselective fungal glycosylation catalyzed by two Absidia species and Beauveria bassiana . As a result six glycosides ( 4 - 9 ) were formed, of which four glycosides ( 6 - 9 ) have not been published so far. The influence of flavonoid skeleton and the presence of glucopyranose and 4- O -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 ( 1 ) 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 ( 2 ) and aurone ( 3 ). 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.