Synthesis, <i>α</i>-Glucosidase inhibition and molecular docking studies of tyrosol derivatives

Abstract

To find a potent <i>α</i>-glucosidase inhibitor, 24 tyrosol derivatives with different substituents located at the <i>meta</i>, <i>ortho</i>, or <i>para</i> position of the phenyl group have been synthesised via the Mitsunobu reaction, characterised by ¹H NMR, ¹³C NMR, ESI-MS and IR and evaluated for inhibition. The derivatives possessed varying degrees of <i>in vitro</i> inhibitory activity against <i>α</i>-glucosidase and a relationship between the structure and activity was subsequently established for all compounds. Two of these compounds with substituents at the <i>para</i> position showed significant inhibitory effects surpassing that of the control standard acarbose. Molecular docking studies performed to better understand the binding interactions between the enzyme and the two most active compounds showed substantial binding within the active site of <i>α</i>-glucosidase. Taken together, these results indicate that the position of the substituent plays a crucial role in this inhibition and may facilitate the development of new <i>α</i>-glucosidase inhibitors.