Synthesis and biological assessment of KojoTacrines as new agents for Alzheimer's disease therapy.
Acetylcholinesterase
/ metabolism
Alzheimer Disease
/ drug therapy
Cholinesterase Inhibitors
/ chemical synthesis
Dose-Response Relationship, Drug
Drug Design
Humans
Models, Molecular
Molecular Structure
Neuroprotective Agents
/ chemical synthesis
Structure-Activity Relationship
Tacrine
/ chemical synthesis
Alzheimer disease
kojic acid
multitarget small molecules
tacrine
Journal
Journal of enzyme inhibition and medicinal chemistry
ISSN: 1475-6374
Titre abrégé: J Enzyme Inhib Med Chem
Pays: England
ID NLM: 101150203
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
entrez:
29
11
2018
pubmed:
30
11
2018
medline:
3
1
2019
Statut:
ppublish
Résumé
In view of the multifactorial nature of Alzheimer's disease (AD), multitarget small molecules (MTSM) represent the most potent and attractive therapeutic strategy to design new drugs for Alzheimer's disease therapy. The new MTSM KojoTacrines (KTs) were designed and synthesized by juxtaposition of selected pharmacophoric motifs from kojic acid and tacrine. Among them, 11-amino-2-(hydroxymethyl)-12-(3-methoxyphenyl)-7,9,10,12-tetrahydropyrano [2',3':5,6] pyrano[2,3-b]quinolin-4(8H)-one (KT2d) was identified as less-hepatotoxic than tacrine, at higher concentration, a moderate, but selective human acetylcholinesterase inhibitor (IC
Identifiants
pubmed: 30482062
doi: 10.1080/14756366.2018.1538136
pmc: PMC6263107
doi:
Substances chimiques
Cholinesterase Inhibitors
0
Neuroprotective Agents
0
Tacrine
4VX7YNB537
Acetylcholinesterase
EC 3.1.1.7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
163-170Références
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