Tetrahydropyranodiquinolin-8-amines as new, non hepatotoxic, antioxidant, and acetylcholinesterase inhibitors for Alzheimer's disease therapy
Language English Country France Media print-electronic
Document type Journal Article
PubMed
27918993
DOI
10.1016/j.ejmech.2016.11.050
PII: S0223-5234(16)30988-6
Knihovny.cz E-resources
- Keywords
- Acetylcholinesterase inhibitors, Alzheimer's disease, Antioxidants, Brain blood barrier, Hepatotoxicity, Molecular modeling, Multifunctional agents,
- MeSH
- Acetylcholinesterase MeSH
- Alzheimer Disease drug therapy MeSH
- Aminoquinolines chemical synthesis pharmacology MeSH
- Antioxidants chemistry pharmacology MeSH
- Cholinesterase Inhibitors chemistry pharmacology MeSH
- GPI-Linked Proteins antagonists & inhibitors MeSH
- Blood-Brain Barrier metabolism MeSH
- Chemical and Drug Induced Liver Injury MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Acetylcholinesterase MeSH
- ACHE protein, human MeSH Browser
- Aminoquinolines MeSH
- Antioxidants MeSH
- Cholinesterase Inhibitors MeSH
- GPI-Linked Proteins MeSH
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.
Biomedical Research Center University Hospital Hradec Kralove Czechia
Laboratory of Medicinal Chemistry C Juan de la Cierva 3 28006 Madrid Spain
References provided by Crossref.org
Carltonine-derived compounds for targeted butyrylcholinesterase inhibition
Synthesis and biological assessment of KojoTacrines as new agents for Alzheimer's disease therapy
