Bis-huperzine B: Highly potent and selective acetylcholine sterase inhibitors

被引：54

作者：

Feng, S ^{[1
]}

Wang, ZF ^{[1
]}

He, XC ^{[1
]}

Zheng, SX ^{[1
]}

Xia, Y ^{[1
]}

Jiang, HL ^{[1
]}

Tang, XC ^{[1
]}

Bai, DL ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 03期

关键词：

D O I：

10.1021/jm0496178

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

By targeting dual active sites of AChE, a series of bis-huperzine B analogues with various lengths of the tether were designed, synthesized, and tested for their inhibition and selectivity. The most potent bis-huperzine B (5g) exhibited 3900-fold increase in AChE inhibition and 930-fold greater in selectivity for AChE vs BuChE than its parent huperzine B.

引用

页码：655 / 657

页数：3

共 21 条

[1] Huperzine A, a potential therapeutic agent for treatment of Alzheimer's disease [J].

Bai, DL ;

Tang, XC ;

He, XC .

CURRENT MEDICINAL CHEMISTRY, 2000, 7 (03) :355-374

[2]

Carlier PR, 2000, ANGEW CHEM INT EDIT, V39, P1775, DOI 10.1002/(SICI)1521-3773(20000515)39:10<1775::AID-ANIE1775>3.0.CO

[3]

2-Q

[4] Evaluation of short-tether bis-THA AChE inhibitors. A further test of the dual binding site hypothesis [J].

Carlier, PR ;

Han, YF ;

Chow, ESH ;

Li, CPL ;

Wang, H ;

Lieu, TX ;

Wong, HS ;

Pang, YP .

BIOORGANIC & MEDICINAL CHEMISTRY, 1999, 7 (02) :351-357

[5] Comparative studies of huperzine A, E2020, and tacrine on behavior and cholinesterase activities [J].

Cheng, DH ;

Tang, XC .

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1998, 60 (02) :377-386

[6] X-ray structures of Torpedo californica acetylcholinesterase complexed with (+)-Huperzine A and (-)-huperzine B:: Structural evidence for an active site rearrangement [J].

Dvir, H ;

Jiang, HL ;

Wong, DM ;

Harel, M ;

Chetrit, M ;

He, XC ;

Jin, GY ;

Yu, GL ;

Tang, XC ;

Silman, I ;

Bai, DL ;

Sussman, JL .

BIOCHEMISTRY, 2002, 41 (35) :10810-10818

[7] A NEW AND RAPID COLORIMETRIC DETERMINATION OF ACETYLCHOLINESTERASE ACTIVITY [J].

ELLMAN, GL ;

COURTNEY, KD ;

ANDRES, V ;

FEATHERSTONE, RM .

BIOCHEMICAL PHARMACOLOGY, 1961, 7 (02) :88-&

[8]

Ewing TJA, 1997, J COMPUT CHEM, V18, P1175, DOI 10.1002/(SICI)1096-987X(19970715)18:9<1175::AID-JCC6>3.0.CO

[9]

2-O

[10]

HIEBLE JP, 1995, PRINCIPLES PHARM BAS, P145

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