Synthesis of novel flavonoid alkaloids as α-glucosidase inhibitors

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 alpha-glucosidase, among which compound 23 was found to show the lowest IC50 of 4.13 mu M. Kinetic analysis indicates that the synthesized compounds 15 and 23 inhibit the enzyme in a non-competitive model with Ki value of 37.8 +/- 0.8 mu M and 13.2 +/- 0.6 mu M. 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. (C) 2017 Elsevier Ltd. All rights reserved.