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

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 18; p. 4064
• Main Authors: Tran, Thai-Son, Tran, Thanh-Dao, Tran, The-Huan, Mai, Thanh-Tan, Nguyen, Ngoc-Le, Thai, Khac-Minh, Le, Minh-Tri
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05.09.2020; MDPI
• Subjects: Acetylcholinesterase; Acetylcholinesterase - chemistry; Acetylcholinesterase - metabolism; Alzheimer's disease; Aspartic Acid Endopeptidases - antagonists & inhibitors; Aspartic Acid Endopeptidases - chemistry; Aspartic Acid Endopeptidases - metabolism; Biological activity; Biological effects; Cholinesterase Inhibitors - pharmacology; Computer Simulation; docking; Enzymes; flavone; Flavones; Flavones - chemical synthesis; Flavones - chemistry; Flavones - pharmacology; Flavonoids; Hydrogen bonds; in silico; in vitro; Ligands; Linear Models; Molecular docking; Molecular Docking Simulation; NMR; Nuclear magnetic resonance; Pathogenesis; QSAR; Quantitative Structure-Activity Relationship; Secretase; β-Site APP-cleaving enzyme 1; β-Site APP-cleaving enzymes; docking; QSAR; in vitro; β-secretase; acetylcholinesterase; in silico; flavone
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25184064

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 ( , , , , and ) had completely new structures. The AChE and BACE-1 inhibitory activities were tested, giving pIC 3.47-4.59 (AChE) and 4.15-5.80 (BACE-1). Three compounds ( , and ) 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.