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

Research output: Contribution to journalArticle

82 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 languageEnglish (US)
Pages (from-to)1775-1777
Number of pages3
JournalAngewandte Chemie - International Edition
Volume39
Issue number10
DOIs
StatePublished - May 15 2000

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Dimerization
Acetylcholinesterase
Biological Products
Pharmaceutical Preparations
huperzine A

Keywords

  • Dimerizations
  • Drug research
  • Enzyme inhibitors
  • Natural products
  • Noncovalent interactions

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Dimerization of an inactive fragment of Huperzine A produces a drug with twice the potency of the natural product. / Carlier, Paul R.; Du, Da Ming; Han, Yi Fan; Liu, Jing; Perola, Emanuele; Williams, Ian D.; Pang, Yuan-Ping.

In: Angewandte Chemie - International Edition, Vol. 39, No. 10, 15.05.2000, p. 1775-1777.

Research output: Contribution to journalArticle

Carlier, Paul R. ; Du, Da Ming ; Han, Yi Fan ; Liu, Jing ; Perola, Emanuele ; Williams, Ian D. ; Pang, Yuan-Ping. / Dimerization of an inactive fragment of Huperzine A produces a drug with twice the potency of the natural product. In: Angewandte Chemie - International Edition. 2000 ; Vol. 39, No. 10. pp. 1775-1777.
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