Novel coumarin derivatives bearing N-benzyl pyridinium moiety: potent and dual binding site acetylcholinesterase inhibitors

Bioorg Med Chem. 2012 Dec 15;20(24):7214-22. doi: 10.1016/j.bmc.2012.08.052. Epub 2012 Sep 7.

Abstract

A novel series of coumarin derivatives linked to benzyl pyridinium group were synthesized and biologically evaluated as inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The enzyme inhibitory activity of synthesized compounds was measured using colorimetric Ellman's method. It was revealed that compounds 3e, 3h, 3l, 3r and 3s have shown higher activity compared with donepezil hydrochloride as standard drug. Most of the compounds in these series had nanomolar range IC(50) in which compound 3r (IC(50) = 0.11 nM) was the most active compound against acetylcholinesterase enzyme.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / pharmacology*
  • Coumarins / chemistry*
  • Coumarins / pharmacology*
  • Electrophorus / metabolism
  • Models, Molecular
  • Pyridinium Compounds / chemistry*
  • Pyridinium Compounds / pharmacology*
  • Structure-Activity Relationship

Substances

  • Cholinesterase Inhibitors
  • Coumarins
  • Pyridinium Compounds