Drug Design of Inhibitors of Alzheimer's Disease (AD): POM and DFT Analyses of Cholinesterase Inhibitory Activity of ß-amino di-Carbonyl Derivatives.
Mini Rev Med Chem
; 19(8): 688-705, 2019.
Article
em En
| MEDLINE
| ID: mdl-30387392
ABSTRACT
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:
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 ANDCONCLUSION:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desenho de Fármacos
/
Inibidores da Colinesterase
/
Doença de Alzheimer
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article