Quinoxalinetacrine QT78, a cholinesterase inhibitor as a potential ligand for Alzheimer’s disease therapy

Eva Ramos, Alejandra Palomino-Antolín, Manuela Bartolini, Isabel Iriepa, Ignacio Moraleda, Daniel Diez-Iriepa, Abdelouahid Samadi, Carol V. Cortina, Mourad Chioua, Javier Egea, Alejandro Romero, José Marco-Contelles

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

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.

Original languageEnglish
Article number1503
JournalMolecules
Volume24
Issue number8
DOIs
Publication statusPublished - Apr 17 2019

Keywords

  • Alzheimer’s disease
  • Cholinesterase inhibitor
  • Hepatotoxicity
  • Molecular modeling
  • Neuroprotection
  • Quinoxalines
  • Quinoxalinetacrines
  • Tacrine

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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