Synthesis and biological evaluation of coumarin derivatives as α-glucosidase inhibitors.

In this study, two series of coumarin derivatives 5a∼i and 6a∼i were synthesized, and their inhibitory activity against α-glucosidase was determined. The results indicated that most of the synthesized derivatives exhibited prominent inhibitory activities against α-glucosidase. Among them, compounds 5a and 5b showed the strongest inhibition with the IC50 values of 19.64 µM and 12.98 µM, respectively. Enzyme kinetic studies of compounds 5a and 5b proved that their inhibition was reversible and a mixed type. The KI and KIS values of compound 5a were calculated to be 27.39 µM and 13.02 µM, respectively, and the corresponding values for compound 5b being 27.02 µM and 13.65 µM, respectively. The docking studies showed that compound 5b could be inserted into the active pocket of α-glucosidase and form hydrogen bonds with LYS293 to enhance the binding affinity.

Synthesis and biological evaluation of novel ursolic acid analogues as potential α-glucosidase inhibitors.

Ursolic acid (UA) is a major pentacyclic triterpenoid in plants, vegetables and fruits, which has been reported to have a potential anti-diabetic activity. Despite various semi-synthetic ursolic acid derivatives already described, new derivatives still need to be designed and synthesized to further improve the anti-diabetic activity. In the present study, two series of novel UA derivatives, were synthesized and their structures were confirmed. The enzyme inhibition activities of semi-synthesized analogues against α-glucosidase were screened in vitro. The results indicated that most of UA derivatives showed a significant inhibitory activity, especially analogues UA-O-i with the IC50 values of 0.71 ± 0.27 µM, which was more potential than other analogues and the positive control. Furthermore, molecular docking studies were also investigated to verify the in vitro study. Structure modification at the C-3 and C-2 positions of UA was an effective approach to obtain the desired ligand from UA, whose structure was in accordance with the active pocket. Besides, suitable hydrophobic group at the position of C-2 might play an important role for the docking selectivity and binding affinity between the ligand and the homology modelling protein. These results could be helpful for designing more potential α-glucosidase inhibitors from UA in the future.