Racemic N1-norphenserine and its enantiomers: Unpredicted inhibition of human acetyl- and butyrylcholinesterase and β-amyloid precursor protein in vitro

Qian Sheng Yu, Weiming Luo, Harold W. Holloway, Tada Utsuki, Tracy Ann Perry, Debomoy Lahiri, Nigel H. Greig, Arnold Brossi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The optically pure enantiomers of N1-norphenserine (15, 16) were synthesized and its racemate 17 was prepared by mixing equal parts of each enantiomer. (-)-N1-Norphenserine (15) was prepared by partial synthesis initiated from the natural product, (-)-physostigmine (1). (+)-N 1-Norphenserine (16) was prepared by total synthesis using the Julian oxindole route, with modifications. The in vitro inhibitory activities of 15-17 were quantified against human erythrocyte AChE and plasma BChE as well as against human neuroblastoma cell β-amyloid precursor protein secretion in cell culture. All were active. Racemic compound (17) with a high AChE and β-amyloid precursor protein inhibitory action may warrant further assessment in Alzheimer's disease models.

Original languageEnglish
Pages (from-to)529-539
Number of pages11
JournalHeterocycles
Volume61
StatePublished - Dec 31 2003

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Butyrylcholinesterase
Enantiomers
Amyloid beta-Protein Precursor
Acetylcholinesterase
Physostigmine
Biological Products
Neuroblastoma
Cell culture
Alzheimer Disease
Cell Culture Techniques
Erythrocytes
Plasmas
In Vitro Techniques
Inhibition (Psychology)
compound 17
oxindole

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Racemic N1-norphenserine and its enantiomers : Unpredicted inhibition of human acetyl- and butyrylcholinesterase and β-amyloid precursor protein in vitro. / Yu, Qian Sheng; Luo, Weiming; Holloway, Harold W.; Utsuki, Tada; Perry, Tracy Ann; Lahiri, Debomoy; Greig, Nigel H.; Brossi, Arnold.

In: Heterocycles, Vol. 61, 31.12.2003, p. 529-539.

Research output: Contribution to journalArticle

Yu, Qian Sheng ; Luo, Weiming ; Holloway, Harold W. ; Utsuki, Tada ; Perry, Tracy Ann ; Lahiri, Debomoy ; Greig, Nigel H. ; Brossi, Arnold. / Racemic N1-norphenserine and its enantiomers : Unpredicted inhibition of human acetyl- and butyrylcholinesterase and β-amyloid precursor protein in vitro. In: Heterocycles. 2003 ; Vol. 61. pp. 529-539.
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