Design, synthesis and α-glucosidase inhibition study of novel embelin derivatives.

Embelin is a naturally occurring -benzoquinone isolated from (Burm. f.) of the Myrsinaceae family. It was first discovered to have potent inhibitory activity (IC = 4.2 μM) against α-glucosidase in this study. Then, four series of novel embelin derivatives were designed, prepared and evaluated in α-glucosidase inhibition assays. The results show that most of the embelin derivatives synthesised are effective α-glucosidase inhibitors, with IC values at the micromolar level, especially , , and , the IC values of which are 1.8, 3.3, and 3.6 μM, respectively. Structure-activity relationship (SAR) studies suggest that hydroxyl groups in the 2/5-position of -benzoquinone are very important, and long-chain substituents in the 3-position are highly preferred. Moreover, the inhibition mechanism and kinetics studies reveal that all of , , , and embelin are reversible and mixed-type inhibitors. Furthermore, docking experiments were carried out to study the interactions between and with α-glucosidase.