Piceid dicarboxylic acid esters as potent α-glucosidase inhibitors and antiglycation agents: Synthesis, spectroscopic and molecular docking studies

s Inhibition of α-glucosidase and non-enzymatic glycation is an effective approach to treat type 2 diabetes. Piceid (PI) is a potential α-glucosidase inhibitor and antiglycation agent found in many plant-based foods and herbs. To enhance the liposolubility and hypoglycemic effects of PI, two PI dicarboxylic acid esters were synthesized via enzymatic acylation in green solvents using dicarboxylic acids with hypoglycemic activity as acyl donors. Their structures were characterized by HPLC, HRMS, and 13 C NMR. Also, the antiglycation and α-glucosidase inhibitory effects of PI derivatives were investigated by enzymatic kinetics, CD, bovine serum albumin (BSA)-fructose model, FTIR, and molecular docking analysis. The results found that the introduction of dicarboxylic acid molecules significantly enhanced liposolubility, antiglycation, and α-glucosidase inhibitory activities of PI. The IC 50 values of two PI derivatives on α-glucosidase were nearly 9.9-fold and 16.2-fold lower than native PI, respectively. Moreover, the dicarboxylic acid moieties in PI derivatives induced the conformational changes of α-glucosidase, which made the secondary structure of α-glucosidase tighter, thus hindering the entry of substrates. Molecular docking results showed that PI derivatives could insert into the active pocket of α-glucosidase and interact with more key amino acid residues than PI. Also, PI derivatives could block the glycation sites of BSA.