Synthesis and biological assessment of KojoTacrines as new agents for Alzheimer's disease therapy.
J Enzyme Inhib Med Chem
; 34(1): 163-170, 2019 Dec.
Article
in En
| MEDLINE
| ID: mdl-30482062
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 (IC50 = 4.52 ± 0.24 µM), as well as an antioxidant agent (TE = 4.79) showing significant neuroprotection against Aß1-40 at 3 µM and 10 µM concentrations. Consequently, KT2d is a potential new hit-ligand for AD therapy for further biological exploration.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tacrine
/
Cholinesterase Inhibitors
/
Neuroprotective Agents
/
Alzheimer Disease
Limits:
Humans
Language:
En
Journal:
J Enzyme Inhib Med Chem
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2019
Document type:
Article
Affiliation country:
Tunisia
Country of publication:
United kingdom