2-Phenylbenzofuran derivatives as butyrylcholinesterase inhibitors: Synthesis, biological activity and molecular modeling

Bioorg Med Chem Lett. 2016 May 1;26(9):2308-13. doi: 10.1016/j.bmcl.2016.03.039. Epub 2016 Mar 11.


A series of 2-phenylbenzofurans compounds was designed, synthesized and evaluated as cholinesterase inhibitors. The biological assay experiments showed that most of the compounds displayed a clearly selective inhibition for butyrylcholinesterase (BChE), while a weak or no effect towards acetylcholinesterase (AChE) was detected. Among these benzofuran derivatives, compound 16 exhibited the highest BChE inhibition with an IC50 value of 30.3 μM. This compound was found to be a mixed-type inhibitor as determined by kinetic analysis. Moreover, molecular dynamics simulations revealed that compound 16 binds to both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of BChE and it displayed the best interaction energy value, in agreement with our experimental data.

Keywords: Acetylcholinesterase; Alzheimer’s disease; Benzofurans; Butyrylcholinesterase; Cholinesterase inhibitors; Docking; Molecular dynamics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzofurans / chemical synthesis*
  • Benzofurans / chemistry
  • Benzofurans / pharmacology*
  • Butyrylcholinesterase / drug effects*
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Models, Molecular


  • Benzofurans
  • Cholinesterase Inhibitors
  • Butyrylcholinesterase
  • benzofuran