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Synthesis, In Silico and In Vitro Evaluation of Some Flavone Derivatives for Acetylcholinesterase and BACE-1 Inhibitory Activity

Acetylcholinesterase (AChE) and β-secretase (BACE-1) have become attractive therapeutic targets for Alzheimer’s disease (AD). Flavones are flavonoid derivatives with various bioactive effects, including AChE and BACE-1 inhibition. In the present work, a series of 14 flavone derivatives was synthesiz...

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Detalles Bibliográficos
Autores principales: Tran, Thai-Son, Tran, Thanh-Dao, Tran, The-Huan, Mai, Thanh-Tan, Nguyen, Ngoc-Le, Thai, Khac-Minh, Le, Minh-Tri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570966/
https://www.ncbi.nlm.nih.gov/pubmed/32899576
http://dx.doi.org/10.3390/molecules25184064
Descripción
Sumario:Acetylcholinesterase (AChE) and β-secretase (BACE-1) have become attractive therapeutic targets for Alzheimer’s disease (AD). Flavones are flavonoid derivatives with various bioactive effects, including AChE and BACE-1 inhibition. In the present work, a series of 14 flavone derivatives was synthesized in relatively high yields (35–85%). Six of the synthetic flavones (B4, B5, B6, B8, D6 and D7) had completely new structures. The AChE and BACE-1 inhibitory activities were tested, giving pIC(50) 3.47–4.59 (AChE) and 4.15–5.80 (BACE-1). Three compounds (B3, D5 and D6) exhibited the highest biological effects on both AChE and BACE-1. A molecular docking investigation was conducted to explain the experimental results. These molecules could be employed for further studies to discover new structures with dual action on both AChE and BACE-1 that could serve as novel therapies for AD.