Design, synthesis and anti-Alzheimer's activity of novel 1,2,3-triazole-chromenone carboxamide derivatives.
Bioorg Chem
; 83: 391-401, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30412794
ABSTRACT
Alzheimer's disease (AD) is a well-known neurodegenerative disorder affecting millions of old people worldwide and the corresponding epidemiological data highlights the significance of the disease. As AD is a multifactorial illness, various single-target directed drugs that have reached clinical trials have failed. Therefore, various factors associated with outset of AD have been considered in targeted drug discovery and development. In this work, a wide range of 1,2,3-triazole-chromenone carboxamides were designed, synthesized, and evaluated for their cholinesterase inhibitory activity. Among them, N-(1-benzylpiperidin-4-yl)-7-((1-(3,4-dimethylbenzyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-oxo-2H-chromene-3-carboxamide (11b) showed the best acetylcholinesterase inhibitory activity (IC50â¯=â¯1.80⯵M), however, it was inactive toward butyrylcholinesterase. It should be noted that compound 11b was evaluated for its BACE1 inhibitory activity and calculated IC50â¯=â¯21.13⯵M confirmed desired inhibitory activity. Also, this compound revealed satisfactory neuroprotective effect against H2O2-induced cell death in PC12 neurons at 50⯵M as well as metal chelating ability toward Fe2+, Cu2+, and Zn2+ ions.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Triazóis
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Fármacos Neuroprotetores
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Cumarínicos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Irã