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Bioorg Med Chem Lett ; 27(2): 232-236, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-27923619

RESUMO

The design, synthesis and assessment of ß-carboline core-based compounds as potential multifunctional agents against several processes that are believed to play a significant role in Alzheimer's disease (AD) pathology, are described. The activity of the compounds was determined in Aß self-assembly (fibril and oligomer formation) and cholinesterase (AChE, BuChE) activity inhibition, and their antioxidant properties were also assessed. To obtain insight into the mode of action of the compounds, HR-MS studies were carried out on the inhibitor-Aß complex formation and molecular docking was performed on inhibitor-BuChE interactions. While several compounds exhibited strong activities in individual assays, compound 14 emerged as a promising multi-target lead for the further structure-activity relationship studies.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/análise , Antioxidantes/farmacologia , Carbolinas/farmacologia , Inibidores da Colinesterase/farmacologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/biossíntese , Antioxidantes/síntese química , Antioxidantes/química , Carbolinas/síntese química , Carbolinas/química , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Colinesterases/metabolismo , Relação Dose-Resposta a Droga , Desenho de Fármacos , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade
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