Design, synthesis and anticholinesterase activity of novel benzylidenechroman-4-ones bearing cyclic amine side chain

Eur J Med Chem. 2015 Jun 5:97:181-9. doi: 10.1016/j.ejmech.2015.04.055. Epub 2015 Apr 29.

Abstract

A series of 3-(4-(aminoalkoxy)benzylidene)-chroman-4-ones 7a-r were designed and synthesized as analogs of homoisoflavonoids which are well known natural products with diverse pharmacological properties related to Alzheimer's disease. The in vitro anti-cholinesterase activity of designed compounds 7a-r against AChE and BuChE, revealed that compounds bearing piperidinylethoxy residue showed potent activity against AChE at sub-micromolar level (IC50 values = 0.122-0.207 μM), more potent than reference drug tacrine. The structure-activity relationships study of piperidinylethoxy series demonstrated that the selectivity and physicochemical properties of compounds could be optimized by selection of a proper substituent on the C-7 position of chroman ring, while the high potency of the molecule against AChE was reserved.

Keywords: Acetylcholinesterase; Alzheimer's disease; Chroman-4-one; Docking study; Homoisoflavonoids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemical synthesis*
  • Amines / chemistry
  • Amines / pharmacology
  • Benzylidene Compounds / chemical synthesis*
  • Benzylidene Compounds / chemistry
  • Benzylidene Compounds / pharmacology
  • Catalytic Domain
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology
  • Chromones / chemical synthesis*
  • Chromones / chemistry
  • Chromones / pharmacology
  • Cyclization
  • Drug Design*
  • Inhibitory Concentration 50
  • Models, Molecular

Substances

  • Amines
  • Benzylidene Compounds
  • Cholinesterase Inhibitors
  • Chromones