Synthesis and anti-α-glucosidase activity evaluation of betulinic acid derivatives

In this article, a series of betulinic acid derivatives (3a∼3u, 4a∼4e) were synthesized through a stepwise structure optimization and evaluated for their anti-α-glucosidase activities. All synthesized derivatives exhibited stronger anti-α-glucosidase activities (IC50: 0.56 ± 0.05 ∼ 3.99 ± 0.23 μM) than betulinic acid (IC50: 7.21 ± 0.58 μM) and acarbose (IC50: 611.45 ± 15.51 μM). Compound 3q presented the outstanding inhibitory activity (IC50: 0.56 ± 0.05 μM), which was ∼1100 time stronger than that of acarbose. Compound 3q was revealed as a reversible and noncompetitive α-glucosidase inhibitor by inhibitory mechanism assay. Fluorescence spectra, 3D fluorescence and CD spectra results showed that the interaction of compound 3q with α-glucosidase caused the conformational and secondary structure content change of α-glucosidase. Finally, the molecular docking simulated the interaction between compound 3q with α-glucosidase and the physicochemical parameter was assessed using SwissADME software.