BACE1 inhibitory effects of lavandulyl flavanones from Sophora flavescens Original Research Article

In order to access β-secretase (BACE1), and enzyme strongly implicated in the cause of Alzheimer’s disease, inhibitors must possess sufficient lipophilicity to traverse two lipid bilayers. Current drug candidates, which are almost totally peptide-derived, are thus inefficient because cell permeability presents a serious limiting factor. In this study, lipophilic alkylated (C10–C5) flavanones from Sophora flavescens were examined for their inhibitory effects against β-secretase. Lavandulyl flavanones (1, 2, 5, 6, and 8) showed potent β-secretase inhibitory activities with IC50s of 5.2, 3.3, 8.4, 2.6, and 6.7 μM, respectively, while no significant activity was observed in the corresponding hydrated lavandulyl flavanones (4 and 7) and prenylated flavanone (3). As we expected, lavandulyl flavanones reduced Aβ secretion dose-dependently in transfected human embryonic kidney (HEK-293) cells. In kinetic studies, all compounds screened were shown to be noncompetitive inhibitor.