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; Yi Fan Han; Jing Liu; Emanuele Perola; Ian D. Williams; Yuan Ping Pang

doi:10.1002/(SICI)1521-3773(20000515)39:10<1775::AID-ANIE1775>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, Yi Fan Han, Jing Liu, Emanuele Perola, Ian D. Williams, Yuan Ping Pang

Pharmacology

Research output: Contribution to journal › Article › peer-review

83 Scopus citations

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 (US)
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
State	Published - May 15 2000

Keywords

Dimerizations
Drug research
Enzyme inhibitors
Natural products
Noncovalent interactions

ASJC Scopus subject areas

Catalysis
General Chemistry

Access to Document

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

Cite this

@article{9d584b4780684af884c529b56deca9f4,

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

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.",

keywords = "Dimerizations, Drug research, Enzyme inhibitors, Natural products, Noncovalent interactions",

author = "Carlier, {Paul R.} and Du, {Da Ming} and Han, {Yi Fan} and Jing Liu and Emanuele Perola and Williams, {Ian D.} and Pang, {Yuan Ping}",

year = "2000",

month = may,

day = "15",

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

language = "English (US)",

volume = "39",

pages = "1775--1777",

journal = "Angewandte Chemie - International Edition",

issn = "1433-7851",

publisher = "John Wiley and Sons Ltd",

number = "10",

}

TY - JOUR

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, Yi Fan

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 - http://www.scopus.com/inward/record.url?scp=0034657522&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034657522&partnerID=8YFLogxK

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 - Article

AN - SCOPUS:0034657522

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

Access to Document

Other files and links

Fingerprint

Cite this