-Glucosidase Inhibition Research of Derivatives Based on 2-Acetoxyferruginol Scaffold Excluding Acetic Acid Group

In this study, a series derivatives based on 2 beta-acetoxyferruginol scaffold excluding acetic acid group (1 similar to 24) were synthesized and their inhibitory activities on a-glucosidase were determined. The results showed that all compounds 1 similar to 24 had good a-glucosidase inhibitory activities. Among them, (3R,4aS,10aS)-6-hydroxy-1,1,4a-trimethyl-1,2,3,4,4a,9,10,10a-octahy-drophenanthren3-yl 4-(trifluoromethyl)benzoate (15) had the strongest inhibitory activity [IC50=( 23.91 +/- 2.34) mu mol/L], about 23.6-fold more active than acarbose. The structure activity relationship analysis showed that the introduction of trifluoromethyl was more conducive to enhance its activity. The kinetic results showed that compound 15 was a reversible and non competitive a-glucosidase inhibitor. The 3D fluorescence results indicated that the binding of a-glucosidase with compound 15 could change the conformation of a-glucosidase. The molecular docking results showed that compound 15 made hydrogen bonds with Asp68, Arg312, and Tyr313, and formed hydrophobic interactions with Phe177 and Phe300.