Synthesis, in vitro inhibitory activity, kinetic study and molecular docking of novel N-alkyl-deoxynojirimycin derivatives as potential alpha-glucosidase inhibitors

摘要

A series of novelN-alkyl-1-deoxynojirimycin derivatives25 similar to 44were synthesised and evaluated for their in vitro alpha-glucosidase inhibitory activity to develop alpha-glucosidase inhibitors with high activity. All twenty compounds exhibited alpha-glucosidase inhibitory activity with IC50 values ranging from 30.0 +/- 0.6 mu M to 2000 mu M as compared to standard acarbose (IC50= 822.0 +/- 1.5 mu M). The most active compound43was similar to 27-fold more active than acarbose. Kinetic study revealed that compounds43,40, and34were all competitive inhibitors on alpha-glucosidase withK(i)of 10 mu M, 52 mu M, and 150 mu M, respectively. Molecular docking demonstrated that the high active inhibitors interacted with alpha-glucosidase by four types of interactions, including hydrogen bonds, pi-pi stacking interactions, hydrophobic interactions, and electrostatic interaction. Among all the interactions, the pi-pi stacking interaction and hydrogen bond played a significant role in a various range of activities of the compounds.