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

A series of benzylidene analogs of oleanolic acid 4a∼4s were synthesized and assessed for their α-glucosidase and α-amylase inhibitory activities. The results presented that all synthesized analogs exhibited excellent-to-moderate inhibitory effects on α-glucosidase and α-amylase. Analog 4i showed the highest α-glucosidase inhibition (IC(50): 0.40 μM), and analog 4o presented the strongest α-amylase inhibition (IC(50): 9.59 μM). Inhibition kinetics results showed that analogs 4i and 4o were reversible and mixed-type inhibitors against α-glucosidase and α-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.