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

Molecules. 2020 Sep 5;25(18):4064. 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 (B4, B5, B6, B8, D6 and D7) had completely new structures. The AChE and BACE-1 inhibitory activities were tested, giving pIC50 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.

Keywords: QSAR; acetylcholinesterase; docking; flavone; in silico; in vitro; β-secretase.

MeSH terms

  • Acetylcholinesterase / chemistry
  • Acetylcholinesterase / metabolism*
  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Aspartic Acid Endopeptidases / chemistry
  • Aspartic Acid Endopeptidases / metabolism
  • Cholinesterase Inhibitors / pharmacology*
  • Computer Simulation*
  • Flavones / chemical synthesis*
  • Flavones / chemistry
  • Flavones / pharmacology*
  • Linear Models
  • Molecular Docking Simulation
  • Quantitative Structure-Activity Relationship


  • Cholinesterase Inhibitors
  • Flavones
  • Acetylcholinesterase
  • Aspartic Acid Endopeptidases
  • flavone