Discovery and biological evaluation of novel α-glucosidase inhibitors with in vivo antidiabetic effect

Discovery of α-glucosidase inhibitors has been actively pursued with the aim to develop therapeutics for the treatment of diabetes and the other carbohydrate-mediated diseases. We have identified four novel α-glucosidase inhibitors by means of a drug design protocol involving the structure-based virtual screening under consideration of the effects of ligand solvation in the scoring function and in vitro enzyme assay. Because the newly identified inhibitors reveal in vivo antidiabetic activity as well as a significant potency with more than 70% inhibition of the catalytic activity of α-glucosidase at 50 μM, all of them seem to deserve further development to discover new drugs for diabetes. Structural features relevant to the interactions of the newly identified inhibitors with the active site residues of α-glucosidase are discussed in detail.