Synthesis and evaluation of cinnamic acid derivatives as ɑ- glucosidase inhibitors

Abstract

Six cinnamic acid derivatives (1 ~ 6) were synthesized for finding potential α-glucosidase inhibitors. The structure of derivatives (1 ~ 6) were confirmed by NMR and HRMS. Inhibitory activity screening results showed that cinnamic acid derivatives (1 ~ 6) exhibited potential α-glucosidase inhibitory activity. Compound 2 showed the highest α-glucosidase inhibitory activity with IC50 value of 39.91 ± 0.62 µM. SAR results showed that introduction of substituent groups in benzene ring of cinnamic acid enhanced the α-glucosidase inhibition activity, and methyl group had the optimal gain. Inhibitory kinetics results showed compound 2 was one reversible and mixed-type inhibitor. Molecular docking results revealed that compound 2 tightly bind to active pocket of α-glucosidase and formed hydrogen bond and hydrophobic interactions with α-glucosidase.