Ent-kaurane glycosides from Stevia rebaudiana and their α-glucosidase inhibition

Phytochemical investigation of the water soluble fraction of the plant Stevia rebaudiana led to isolation of 10 ent-kaurane glycosides, including two new derivatives namely stevibiosides A and B (1 and 2). Their structures were elucidated by extensive analysis of their 1D, 2D NMR, and HRQTOF mass spectra as well as quantum chemical calculations. Conformation studies and DFT-calculated chemical shifts combined with simple (R2, MAE) and DP4+ statistical analyses allow for the complete characterization of compounds 1 and 2. Among isolates, stevibioside A (1) exhibited potent α-glycosidase inhibitory effects with IC50 value of 8.9 ± 0.45 μM. Inhibitory kinetics analysis indicated that 1 had effect with an uncompetitive inhibition type and the Ki value of 2.18 ± 0.81 μM. In addition, docking studies were then used to analysis of the binding modes of the compounds 1 and 2 over the crystallographic structure of yeast α-glucosidase (pdb 3A4A) active site in comparison with acarbose as a standard inhibitor of this enzyme.