α-Glucosidase Inhibition Research of Derivatives Based on 2β-Acetoxyferruginol Scaffold Excluding Acetic Acid Group
In this study,a series derivatives based on 2β-acetoxyferruginol scaffold excluding acetic acid group(1～24)were synthesized and their inhibitory activities on α-glucosidase were determined.The results showed that all compounds 1～24 had good α-glucosidase inhibitory activities.Among them,(3R,4aS,10aS)-6-hydroxy-1,1,4a-trimethyl-1,2,3,4,4a,9,10,10a-octahy-drophenanthren-3-yl 4-(trifluoromethyl)benzoate(15)had the strongest inhibitory activity[ICs0=(23.91±2.34)μmol/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 α-glucosidase inhibitor.The 3D fluorescence results indicated that the binding of α-glucosidase with compound 15 could change the conformation of α-glucosidase.The molecular docking results showed that compound 15 made hydrogen bonds with Asp68,Arg312,andTyr313,and formed hydrophobic interactions with Phel77 and Phe300.
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