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

摘要

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.