Nostocarboline: isolation and synthesis of a new cholinesterase inhibitor from Nostoc 78-12A

J Nat Prod. 2005 Dec;68(12):1793-5. doi: 10.1021/np050312l.

Abstract

A new quaternary beta-carboline alkaloid, nostocarboline, was isolated from the freshwater cyanobacterium Nostoc 78-12A, and its constitution was assigned by 2D-NMR methods. The structure was proven by its total synthesis starting from norharmane via chlorination at C-6 and methylation at N-2. Nostocarboline was found to be a potent butyrylcholinesterase (BChE) inhibitor, with an IC(50) of 13.2 microM. The related 2-methylnorharmane, which is present in the human brain and might be relevant to Parkinson's disease (PD), was also determined to be a BChE inhibitor (11.2 microM). These inhibitory concentrations are comparable to galanthamine, an approved drug for the treatment of Alzheimer's disease (AD). Nostocarboline can thus be considered as a lead for the development of novel neurochemicals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / enzymology
  • Butyrylcholinesterase / metabolism*
  • Carbolines*
  • Cholinesterase Inhibitors* / chemistry
  • Cholinesterase Inhibitors* / isolation & purification
  • Cholinesterase Inhibitors* / pharmacology
  • Galantamine / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Nostoc / chemistry*
  • Parkinson Disease / drug therapy

Substances

  • Carbolines
  • Cholinesterase Inhibitors
  • nostocarboline
  • Galantamine
  • Butyrylcholinesterase