Insights into the α-amylase and α-glucosidase inhibition mechanism of 4-(4-hydroxyphenyl)-but-3-en-2-one from Scutellaria barbata D. Don: enzymatic kinetics, fluorescence spectroscopy and computational simulation

Diabetes mellitus has become a pandemic in modern society. Regulation of carbohydrate hydrolysis by inhibition of key-digestive enzymes is currently used to control hyperglycaemia. Therefore, characterization of safe and efficient alternative therapeutic agents has become essential. Herein, the mechanism of α-amylase and α-glucosidase inhibition of 4-(4-hydroxyphenyl)-but-3-en-2-one ( 4 ) isolated from Scutellaria barbata D. Don was investigated by in vitro enzymatic kinetics, conformation analysis and molecular docking. The results demonstrated that 4-(4-hydroxyphenyl)-but-3-en-2-one ( 4 ) reversibly inhibited α-amylase and α-glucosidase in a mixed-type and competitive manner with IC 50 values of 81.2 ± 5.3 and 54.8 ± 2.4 µM, respectively. Analysis of fluorescence spectroscopy showed that the interaction of the compound with both enzymes was primarily influenced by hydrogen bonding and van der Waals forces, and was a spontaneous process. Moreover, computer modelling indicated that the amino acid residues of the enzymes were bound to the compound mainly by hydrogen bonds. The results indicated that the substituents in the molecular structure of the compounds play a crucial role in the inhibition activity of the compounds. 4-(4-Hydroxyphenyl)-but-3-en-2-one ( 4 ) with methyl vinyl ketone substitution on the benzene ring was the most potent inhibitor for both enzymes. Graphical abstract