Dimerization of an inactive fragment of Huperzine A produces a drug with twice the potency of the natural product

Paul R. Carlier; Da Ming Du; Yifan Han; Jing Liu; Emanuele Perola; Ian D. Williams; Yuan Ping Pang

doi:10.1002/(SICI)1521-3773(20000515)39:10&lt;1775::AID-ANIE1775&gt;3.0.CO;2-Q

Dimerization of an inactive fragment of Huperzine A produces a drug with twice the potency of the natural product

Paul R. Carlier
, Da Ming Du
, Yifan Han
, Jing Liu
, Emanuele Perola
, Ian D. Williams
, Yuan Ping Pang

Research output: Journal article publication › Journal article › Academic research › peer-review

90 Citations (Scopus)

Abstract

Simultaneous binding to the catalytic and peripheral sites of acetylcholinesterase (AChE) is invoked to explain why the new drug (S,S)-(-)- 3, in which two aminoquinolinone units are linked by a dodecamethylene tether, is more than twice as potent as the natural product huperzine A (-)-1 in the inhibition of ACHE. In contrast aminoquinolinone (±)-2, which retains much of the functionality of (-)-1, inhibits AChE only very weakly.

Original language	English
Pages (from-to)	1775-1777
Number of pages	3
Journal	Angewandte Chemie - International Edition
Volume	39
Issue number	10
DOIs	https://doi.org/10.1002/(SICI)1521-3773(20000515)39:10<1775::AID-ANIE1775>3.0.CO;2-Q
Publication status	Published - 15 May 2000
Externally published	Yes

Keywords

Dimerizations
Drug research
Enzyme inhibitors
Natural products
Noncovalent interactions

ASJC Scopus subject areas

Catalysis
General Chemistry

More information

10.1002/(SICI)1521-3773(20000515)39:10<1775::AID-ANIE1775>3.0.CO;2-Q

Cite this

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abstract = "Simultaneous binding to the catalytic and peripheral sites of acetylcholinesterase (AChE) is invoked to explain why the new drug (S,S)-(-)- 3, in which two aminoquinolinone units are linked by a dodecamethylene tether, is more than twice as potent as the natural product huperzine A (-)-1 in the inhibition of ACHE. In contrast aminoquinolinone (±)-2, which retains much of the functionality of (-)-1, inhibits AChE only very weakly.",

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T1 - Dimerization of an inactive fragment of Huperzine A produces a drug with twice the potency of the natural product

AU - Carlier, Paul R.

AU - Du, Da Ming

AU - Han, Yifan

AU - Liu, Jing

AU - Perola, Emanuele

AU - Williams, Ian D.

AU - Pang, Yuan Ping

PY - 2000/5/15

Y1 - 2000/5/15

N2 - Simultaneous binding to the catalytic and peripheral sites of acetylcholinesterase (AChE) is invoked to explain why the new drug (S,S)-(-)- 3, in which two aminoquinolinone units are linked by a dodecamethylene tether, is more than twice as potent as the natural product huperzine A (-)-1 in the inhibition of ACHE. In contrast aminoquinolinone (±)-2, which retains much of the functionality of (-)-1, inhibits AChE only very weakly.

AB - Simultaneous binding to the catalytic and peripheral sites of acetylcholinesterase (AChE) is invoked to explain why the new drug (S,S)-(-)- 3, in which two aminoquinolinone units are linked by a dodecamethylene tether, is more than twice as potent as the natural product huperzine A (-)-1 in the inhibition of ACHE. In contrast aminoquinolinone (±)-2, which retains much of the functionality of (-)-1, inhibits AChE only very weakly.

KW - Dimerizations

KW - Drug research

KW - Enzyme inhibitors

KW - Natural products

KW - Noncovalent interactions

UR - https://www.scopus.com/pages/publications/0034657522

U2 - 10.1002/(SICI)1521-3773(20000515)39:10<1775::AID-ANIE1775>3.0.CO;2-Q

DO - 10.1002/(SICI)1521-3773(20000515)39:10<1775::AID-ANIE1775>3.0.CO;2-Q

M3 - Journal article

SN - 1433-7851

VL - 39

SP - 1775

EP - 1777

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

IS - 10

ER -

Dimerization of an inactive fragment of Huperzine A produces a drug with twice the potency of the natural product

Abstract

Keywords

ASJC Scopus subject areas

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