Synthesis of Benzylidene Analogs of Oleanolic Acid as Potential α-Glucosidase and α-Amylase Inhibitors

A series of benzylidene analogs of oleanolic acid 4a & SIM;4s were synthesized and assessed for their alpha-glucosidase and alpha-amylase inhibitory activities. The results presented that all synthesized analogs exhibited excellent-to-moderate inhibitory effects on alpha-glucosidase and alpha-amylase. Analog 4i showed the highest alpha-glucosidase inhibition (IC50: 0.40 mu M), and analog 4o presented the strongest alpha-amylase inhibition (IC50: 9.59 mu M). Inhibition kinetics results showed that analogs 4i and 4o were reversible and mixed-type inhibitors against alpha-glucosidase and alpha-amylase, respectively. Simulation docking results demonstrated the interaction between analogs and two enzymes. Moreover, analogs 4i and 4o showed a high level of safety against 3T3-L1 and HepG2 cells.