QuinoxalineTacrine QT78, a Cholinesterase Inhibitor as a Potential Ligand for Alzheimer's Disease Therapy

Molecules. 2019 Apr 17;24(8):1503. doi: 10.3390/molecules24081503.

Abstract

We report the synthesis and relevant pharmacological properties of the quinoxalinetacrine (QT) hybrid QT78 in a project targeted to identify new non-hepatotoxic tacrine derivatives for Alzheimer's disease therapy. We have found that QT78 is less toxic than tacrine at high concentrations (from 100 μM to 1 mM), less potent than tacrine as a ChE inhibitor, but shows selective BuChE inhibition (IC50 (hAChE) = 22.0 ± 1.3 μM; IC50 (hBuChE) = 6.79 ± 0.33 μM). Moreover, QT78 showed effective and strong neuroprotection against diverse toxic stimuli, such as rotenone plus oligomycin-A or okadaic acid, of biological significance for Alzheimer's disease.

Keywords: Alzheimer’s disease; cholinesterase inhibitor; hepatotoxicity; molecular modeling; neuroprotection; quinoxalines; quinoxalinetacrines; tacrine.

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / enzymology
  • Cholinesterase Inhibitors* / chemistry
  • Cholinesterase Inhibitors* / pharmacokinetics
  • Cholinesterase Inhibitors* / pharmacology
  • Hep G2 Cells
  • Humans
  • Tacrine* / chemistry
  • Tacrine* / pharmacokinetics
  • Tacrine* / pharmacology

Substances

  • Cholinesterase Inhibitors
  • Tacrine