A series of novel flavonoid alkaloids were synthesized with different flavonoids and attached nitrogen-containing moieties. These new compounds were screened for inhibitory activity of á-glucosidase, among which compound 23 was found to show the lowest IC50 of 4.13ìM. Kinetic analysis indicates that the synthesized compounds 15 and 23 inhibit the enzyme in a non-competitive model with Ki value of 37.8±0.8ìM and 13.2±0.6ìM. Further docking studies suggest that the preferred binding pocket is close to the catalytic center, correlating to the experimental results. Structure activity relationship studies (SAR) indicate that 4'-hyroxyl group and the 4-position carbonyl group in the flavonoid structure are important for this biological activity. Addition of extra hydrogen bonding and hydrophobic groups on ring A would increase the inhibitory activity.
Alkaloids Dose-Response Relationship, Drug