Synthesis of 2-(4-hydroxyphenyl)ethyl 3,4,5-Trihydroxybenzoate and Its Inhibitory Effect on Sucrase and Maltase

Abstract

We report on the synthesis of an active component, 2-(4-hydroxyphenyl)ethyl 3,4,5-trihydroxybenzoate (HETB), from Rhodiola crenulata. Subsequent analysis revealed that HETB exhibits α-glucosidase inhibitory activities on maltase and sucrase, with potency exceeding that of the known α-glucosidase inhibitors (voglibose and acarbose). An inhibition kinetics study revealed that HETB, acarbose, and voglibose bind to maltase and sucrase, and HETB was shown to be a strong competitive inhibitor of maltase and sucrase. In a molecular docking study based on the crystal structure of α-glucosidase from Saccharomyces cerevisiae, we revealed the HETB binding in the active site of maltase via hydrogen-bond interactions with five amino acid residues: Ser 240, Asp 242, Glu 277, Arg 315, and Asn 350. For HETB docked to the sucrase active site, seven hydrogen bonds (with Asn 114, Glu 148, Gln 201, Asn 228, Gln 381, Ile 383, and Ser 412) were shown.

Special Issue of “Synthesis, Biological Evaluation and Molecular Modeling of Enzyme Inhibitors”

“…To summarize, the articles included in the Special Issue of "Synthesis, Biological Evaluation and Molecular Modeling of Enzyme Inhibitors" present various applications of molecular docking, modeling, and crystallographic analysis in relation to the biological activity of enzymes and structural properties of their ligands: inhibitors or substrates [13][14][15][16]. SBDD methods, although known and used for a long time, are constantly being developed and improved, providing increasingly detailed data on the ligand-protein interactions that determine enzyme catalytic activity.…”