BACE1 inhibitory effects of lavandulyl flavanones from Sophora flavescens

被引：62

作者：

Hwang, Eun Mi ^{[1
,2
]}

Ryu, Young Bae ^{[3
]}

Kim, Hoi Young ^{[3
]}

Kim, Dong-Gyu ^{[1
,2
]}

Hong, Seong-Geun ^{[1
,2
]}

Lee, Jin Hwan ^{[3
]}

Curtis-Long, Marcus J.

Jeong, Seong Hun ^{[3
]}

Park, Jae-Yong ^{[1
,2
]}

Park, Ki Hun ^{[3
]}

机构：

[1] Gyeongsang Natl Univ, Sch Med, Inst Hlth Sci, Dept Physiol, Jinju 660751, South Korea

[2] Gyeongsang Natl Univ, Grad Sch, Med Res Ctr Neural Dysfunct, Jinju 660701, South Korea

[3] Gyeongsang Natl Univ, Grad Sch, Inst Agr & Life Sci,EB NCRC, Dept Appl Life Sci Program BK21, Jinju 660701, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 14期

关键词：

Alzheimer's disease; BACE1; HEK; 293; lavandulyl flavanone; Sophora flavescens;

D O I：

10.1016/j.bmc.2008.05.080

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

In order to access beta-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 (C(10)-C(5)) flavanones from Sophora flavescens were examined for their inhibitory effects against beta-secretase. Lavandulyl flavanones (1, 2, 5, 6, and 8) showed potent beta-secretase inhibitory activities with IC(50)s of 5.2, 3.3, 8.4, 2.6, and 6.7 mu M, 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 Ab secretion dose-dependently in transfected human embryonic kidney (HEK-293) cells. In kinetic studies, all compounds screened were shown to be noncompetitive inhibitor. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：6669 / 6674

页数：6

共 27 条

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