Novel salicylamide derivatives as potent multifunctional agents for the treatment of Alzheimer's disease: Design, synthesis and biological evaluation.
Bioorg Chem
; 84: 137-149, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30500523
ABSTRACT
A series of salicylamide derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. In vitro assays demonstrated that most of the derivatives were selective AChE inhibitors. They showed good inhibitory activities of self- and Cu2+-induced Aß1-42 aggregation, and significant antioxidant activities. Among them, compound 15b exhibited good inhibitory activity toward RatAChE and EeAChE with IC50 value of 10.4⯵M and 15.2⯵M, respectively. Moreover, 15b displayed high antioxidant activity (2.46 Trolox equivalents), good self- and Cu2+-induced Aß1-42 aggregation inhibitory potency (42.5% and 31.4% at 25.0⯵M, respectively) and moderate disaggregation ability to self- and Cu2+-induced Aß1-42 aggregation fibrils (23.4% and 27.0% at 25⯵M, respectively). Furthermore, 15b also showed biometal chelating abilities, anti-neuroinflammatory ability and BBB permeability. These multifunctional properties indicated compound 15b was worthy of being chosen for further pharmacokinetics, toxicity and behavioral researches to test its potential for AD treatment.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Salicilamidas
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Anti-Inflamatórios não Esteroides
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Inibidores da Colinesterase
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Fármacos Neuroprotetores
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Doença de Alzheimer
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Antioxidantes
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article