Drug Design of Inhibitors of Alzheimer's Disease (AD): POM and DFT Analyses of Cholinesterase Inhibitory Activity of β-amino di-Carbonyl Derivatives.
Alzheimer’s disease (AD)
DFT calculations
Petra/Osiris/
Molinspiration (POM) analysis
cholinesterase inhibition
in vitro
β-Amino dicarbonyl.
Journal
Mini reviews in medicinal chemistry
ISSN: 1875-5607
Titre abrégé: Mini Rev Med Chem
Pays: Netherlands
ID NLM: 101094212
Informations de publication
Date de publication:
2019
2019
Historique:
received:
28
08
2017
revised:
20
01
2018
accepted:
17
03
2018
pubmed:
6
11
2018
medline:
25
6
2019
entrez:
3
11
2018
Statut:
ppublish
Résumé
Since deficit of acetylcholine has been evidenced in the Alzheimer's disease (AD) patients, cholinesterase inhibitors are currently the most specified drug category for the remediation of AD. In the present study, 16 compounds (1-16) with dicarbonyl skeletons have been synthesized and tested for their inhibitory potential in vitro against AChE and BChE using ELISA microtiter plate assays at 100 μg/mL. Since metal accumulation is related to AD, the compounds were also tested for their metal-chelation capacity. All the investigated dicarbonyl compounds exerted none or lower than 30% inhibition against both cholinesterases, whereas compounds 2, 8 and 11 showed 37, 42, 41% of inhibition towards BChE, being the most active. The highest metal-chelation capacity was observed with compound 8 (53.58 ± 2.06%). POM and DFT analyses are in good harmonization with experimental data.
Sections du résumé
BACKGROUND
BACKGROUND
Since deficit of acetylcholine has been evidenced in the Alzheimer's disease (AD) patients, cholinesterase inhibitors are currently the most specified drug category for the remediation of AD.
METHOD
METHODS
In the present study, 16 compounds (1-16) with dicarbonyl skeletons have been synthesized and tested for their inhibitory potential in vitro against AChE and BChE using ELISA microtiter plate assays at 100 μg/mL. Since metal accumulation is related to AD, the compounds were also tested for their metal-chelation capacity.
RESULTS AND CONCLUSION
CONCLUSIONS
All the investigated dicarbonyl compounds exerted none or lower than 30% inhibition against both cholinesterases, whereas compounds 2, 8 and 11 showed 37, 42, 41% of inhibition towards BChE, being the most active. The highest metal-chelation capacity was observed with compound 8 (53.58 ± 2.06%). POM and DFT analyses are in good harmonization with experimental data.
Identifiants
pubmed: 30387392
pii: MRMC-EPUB-94216
doi: 10.2174/1389557518666181102102816
doi:
Substances chimiques
Cholinesterase Inhibitors
0
Acetylcholinesterase
EC 3.1.1.7
Butyrylcholinesterase
EC 3.1.1.8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
688-705Informations de copyright
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