Tetrahydropyranodiquinolin-8-amines as new, non hepatotoxic, antioxidant, and acetylcholinesterase inhibitors for Alzheimer's disease therapy.

Abstract

Herein we report an efficient two step synthesis and biological assessment of 12 racemic tetrahydropyranodiquinolin-8-amines derivatives as antioxidant, cholinesterase inhibitors and non-hepatotoxic agents. Based on the results of the primary screening, we identified 7-(3-methoxyphenyl)-9,10,11,12-tetrahydro-7H-pyrano[2,3-b:5,6-h']diquinolin-8-amine (2h) as a particularly interesting non-hepatotoxic compound that shows moderate antioxidant activity (1.83 equiv Trolox in the ORAC assay), a non competitive inhibition of hAChE (IC50 = 0.75 ± 0.01 μM), and brain permeable as determined by the PAMPA-Blood Brain Barrier assay.

• Authors: Youssef Dgachi, Olga Sokolov, Vincent Luzet, Justyna Godyń, Dawid Panek, Alexandre Bonet, Hélène Martin, Isabel Iriepa, Ignacio Moraleda, Cristina García-Iriepa, Jana Janockova, Lysiane Richert, Ondrej Soukup, Barbara Malawska, Fakher Chabchoub, José Marco-Contelles, Lhassane Ismaili
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 126 Pg. 576-589 (Jan 27 2017) ISSN: 1768-3254 [Electronic] France
• PMID: 27918993 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Chemical References

• Aminoquinolines
• Antioxidants
• Cholinesterase Inhibitors
• GPI-Linked Proteins
• ACHE protein, human
• Acetylcholinesterase

Topics

• Acetylcholinesterase
• Alzheimer Disease (drug therapy)
• Aminoquinolines (chemical synthesis, pharmacology)
• Antioxidants (chemistry, pharmacology)
• Blood-Brain Barrier (metabolism)
• Chemical and Drug Induced Liver Injury
• Cholinesterase Inhibitors (chemistry, pharmacology)
• GPI-Linked Proteins (antagonists & inhibitors)
• Humans