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BACE1 inhibitory effects of lavandulyl flavanones from Sophora flavescens

2008; Elsevier BV; Volume: 16; Issue: 14 Linguagem: Inglês

10.1016/j.bmc.2008.05.080

1464-3391

Eun Mi Hwang, Young Bae Ryu, Hoi Young Kim, Dong-Gyu Kim, Seong-Geun Hong, Jin Hwan Lee, Marcus J. C. Long, Seong Hun Jeong, Jae‐Yong Park, Ki Hun Park,

Retinoids in leukemia and cellular processes

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.