Imidazopyranotacrines as Non-Hepatotoxic, Selective Acetylcholinesterase Inhibitors, and Antioxidant Agents for Alzheimer's Disease Therapy

Molecules. 2016 Mar 24;21(4):400. doi: 10.3390/molecules21040400.

Abstract

Herein we describe the synthesis and in vitro biological evaluation of thirteen new, racemic, diversely functionalized imidazo pyranotacrines as non-hepatotoxic, multipotent tacrine analogues. Among these compounds, 1-(5-amino-2-methyl-4-(1-methyl-1H-imidazol-2-yl)-6,7,8,9-tetrahydro-4H-pyrano[2,3-b]quinolin-3-yl)ethan-1-one (4) is non-hepatotoxic (cell viability assay on HepG2 cells), a selective but moderately potent EeAChE inhibitor (IC50 = 38.7 ± 1.7 μM), and a very potent antioxidant agent on the basis of the ORAC test (2.31 ± 0.29 μmol·Trolox/μmol compound).

Keywords: Alzheimer′s disease; ORAC; antioxidant activity; cholinesterase inhibitors; hepatotoxicity; tacrine analogues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Antioxidants / chemical synthesis*
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology
  • Hep G2 Cells
  • Humans
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Liver / drug effects
  • Oxygen Radical Absorbance Capacity
  • Tacrine / analogs & derivatives
  • Tacrine / chemical synthesis*
  • Tacrine / chemistry
  • Tacrine / pharmacology

Substances

  • Antioxidants
  • Cholinesterase Inhibitors
  • Imidazoles
  • Tacrine