N-1,2,3-triazole-isatin derivatives for cholinesterase and β-amyloid aggregation inhibition: A comprehensive bioassay study

• Autor(a) principal: Marques, Carolina S.
• Data de Publicação: 2020
• Outros Autores: López, Óscar, Bagetta, Donatella, Carreiro, Elisabete P., Petralla, Sabrina, Bartolini, Manuela, Hoffmann, Matthias, Alcaro, Stefano, Monti, Barbara, Bolognesi, Maria Laura, Decker, Michael, Fernández-Bolaños, José, Burke, Anthony J.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10174/31414; https://doi.org/10.1016/j.bioorg.2020.103753
• topic: isatin; oxindole; 1,2,3-triazole; Butyrylcholinesterase; β-amyloid inhibition; Neurotoxicity; Hepatotoxicity

Our goal was the evaluation of a series of N-1,2,3-triazole-isatin derivatives for multi-target activity which included cholinesterase (ChE) inhibition and β-amyloid (Aβ) peptide anti-aggregation. The compounds have shown considerable promise as butyrylcholinesterase (BuChE) inhibitors. Although the inhibition of eel acet- ylcholinesterase (eeAChE) was weak, the inhibitions against equine BuChE (eqBuChE) and human BuChE (hBuChE) were more significant with a best inhibition against eqBuChE of 0.46 μM. In some cases, these mo- lecules gave better inhibitions for hBuChE than eqBuChE. For greater insights into their mode of action, mole- cular docking studies were carried out, followed by STD-NMR validation. In addition, some of these compounds showed weak Aβ anti-aggregation activity. Hepatotoxicity studies showed that they were non-hepatoxic and neurotoxicity studies using neurite out- growth experiments led to the conclusion that these compounds are only weakly neurotoxic.