Synthesis and evaluation of novel rutaecarpine derivatives and related alkaloids derivatives as selective acetylcholinesterase inhibitors

Eur J Med Chem. 2010 Apr;45(4):1415-23. doi: 10.1016/j.ejmech.2009.12.044. Epub 2010 Jan 4.

Abstract

A series of novel rutaecarpine derivatives and related alkaloid derivatives 3-aminoalkanamido-substituted rutaecarpine 4a-f and 7,8-dehydrorutaecarpine 5a-c, and 6-aminoalkanamido-substituted 3-[2-(3-Indolyl)ethyl]-4(3a)-quinazolinones 8a-c, were synthesized and subjected to pharmacological evaluation as acetylcholinesterase (AChE) inhibitors. The synthetic compounds exhibited strong inhibitory activity for AChE and high selectivity for AChE over BuChE. The structure-activity relationships were discussed and their binding conformation and simultaneous interactions mode were further clarified by kinetic characterization and the molecular docking studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / drug effects
  • Alkaloids / chemical synthesis*
  • Alkaloids / chemistry
  • Alkaloids / pharmacology*
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Drug Evaluation, Preclinical
  • Indole Alkaloids / chemical synthesis*
  • Indole Alkaloids / chemistry
  • Indole Alkaloids / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Quinazolines / chemical synthesis*
  • Quinazolines / chemistry
  • Quinazolines / pharmacology*
  • Spectrometry, Mass, Electrospray Ionization
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Cholinesterase Inhibitors
  • Indole Alkaloids
  • Quinazolines
  • rutecarpine
  • Acetylcholinesterase