Hovedulcates A and B, 2,3-dihydrobenzofuran derivatives isolated from the fruits of Hovenia dulcis Thunb. as potential inhibitors of PTP1B and α-glucosidase

From the fruits of Hovenia dulcis Thunb., two new 2,3-dihydrobenzofuran derivatives, named hovedulcates A and B (14 and 16), as well as 20 known compounds (1–13, 15, and 17–22) were isolated. The structures of the isolated compounds were elucidated through a combination of NMR, HR-MS, and ECD spectroscopy analyses, and reported data in the literature. The inhibitory activities of the isolated compounds (1–22) against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase were assessed. Notably, new compounds 14 and 16 exhibited potent inhibitions of both PTP1B and α-glucosidase. The enzyme kinetics analysis was conducted to understand the inhibition mode and inhibitory constants of compounds 14 and 16 for the inhibition of PTP1B and α-glucosidase. Additionally, molecular docking simulations revealed the binding mechanisms and interactions of these compounds with the target enzymes. Our findings suggest that secondary metabolites from H. dulcis fruits are promising natural product treatments for type 2 diabetes.