Synthesis of tacrine-lophine hybrids via one-pot four component reaction and biological evaluation as acetyl- and butyrylcholinesterase inhibitors

Eur J Med Chem. 2013 Apr:62:556-63. doi: 10.1016/j.ejmech.2013.01.029. Epub 2013 Feb 4.

Abstract

A novel series of tacrine-lophine hybrids was synthesized and tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with IC50 in the nanomolar concentration scale. The key step is the one-pot four component condensation reaction of 9-aminoalkylamino-1,2,3,4-tetrahydroacridines, benzil, different substituted aromatic aldehydes and NH4OAc, using InCl3 as the best catalyst. Tacrine-lophine hybrids were found to be potent and selective inhibitors of cholinesterases. As an extension of the four component approach to tetrasubstituted imidazoles, a new series of bis-(2,4,5-triphenyl-1H-imidazoles) or bis(n)-lophines was tested against AChE and BuChE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Animals
  • Butyrylcholinesterase / metabolism*
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Imidazoles / chemistry*
  • Male
  • Molecular Structure
  • Rats
  • Rats, Wistar
  • Structure-Activity Relationship
  • Tacrine / chemistry*

Substances

  • Cholinesterase Inhibitors
  • Imidazoles
  • Tacrine
  • Acetylcholinesterase
  • Butyrylcholinesterase
  • lophine