Xanthones as potential α‐glucosidase non‐competition inhibitors: Synthesis, inhibitory activities, and in silico studies

Abstract

Abstractα‐glucosidase inhibitors (AGIs) were commonly used in clinical for the treatment of type 2 diabetes. Xanthones were naturally occurring antioxidants, and they may also be potential AGIs. In this study, eleven 1,6‐ and 1,3‐substituted xanthone compounds were designed and synthesized, of which four were new compounds. Their α‐glucosidase inhibitory activities in vitro and in silico were evaluated. Five xanthone compounds with higher activity than acarbose were screened out, and the xanthones substituted at the 1,6‐positions were more likely to be potential α‐glucosidase non‐competitive inhibitors. The binding mode of xanthones with α‐glucosidase was further studied by molecular docking method, and the results showed that the inhibitory effect of non‐competitive inhibitors on site 1 of α‐glucosidase may be related to the hydrogen bonds formed by the compounds with amino acid residues ASN165, HIS209, TRY207, ASP243, and SER104. This study provided a theoretical basis of the rapid discovery and structural modification of non‐competitive xanthone inhibitors of α‐glucosidase.