Synthesis and inhibitory activity of euparin derivatives as potential dual inhibitors against α-glucosidase and protein tyrosine phosphatase 1B (PTP1B)

Abstract

Diabetes mellitus is a serious threat to human life and health. The α-glucosidase and protein tyrosine phosphatase 1B (PTP1B) were important targets for the treatment of type 2 diabetes mellitus. In this paper, euparin, a natural product from Eupatorium chinense possessed extensive pharmacological activities, was selected as the lead compound. It was derived into chalcone compounds with high efficiency, and the inhibitory activities of these 30 products on α-glucosidase and PTP1B were tested. The results showed that compounds 12 and 15 had good inhibitory activities against both enzymes. The IC₅₀ value of 12 to inhibit α-glucosidase and PTP1B was 39.77 and 39.31 μM, and the IC₅₀ value of 15 to inhibit α-glucosidase and PTP1B was 9.02 and 3.47 μM, respectively. In addition, molecular docking results showed that compounds 12 and 15 exhibited good binding affinities toward both α -glucosidase and PTP1B with negative binding energies. The results of the present study demonstrate that compounds 12 and 15 might be beneficial in the treatment of type 2 diabetes.

Keywords: Chalcone; Diabetes; Euparin; Molecular docking; PTP1B; α-Glucosidase.