Synthesis, in vitro acetylcholinesterase inhibitory activity and molecular docking of new acridine-coumarin hybrids

Int J Biol Macromol. 2017 Nov;104(Pt A):333-338. doi: 10.1016/j.ijbiomac.2017.06.006. Epub 2017 Jun 7.

Abstract

A novel series of acridine-coumarin hybrids was synthesized and biologically evaluated for their potential inhibitory effect on both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The newly synthesized derivatives 9a-d have shown higher activity against human AChE (hAChE) compared with 7-MEOTA as the standard drug. Among them derivative 9b exhibited the most potent acetylcholinesterase inhibitory activity, with an IC50 value of 5.85μM compared with 7-MEOTA (IC50=15μM). Molecular modelling studies were performed to predict the binding modes of compounds 9b, 9c and 9f with hAChE/hBuChE.

Keywords: Acridine; Alzheimeŕs disease; Cholinesterase; Cholinesterase inhibitors; Coumarin; Tacrine.

MeSH terms

  • Acetylcholinesterase / chemistry
  • Acetylcholinesterase / metabolism*
  • Acridines / chemical synthesis
  • Acridines / chemistry*
  • Acridines / metabolism
  • Acridines / pharmacology*
  • Catalytic Domain
  • Chemistry Techniques, Synthetic
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / metabolism
  • Cholinesterase Inhibitors / pharmacology*
  • Coumarins / chemistry*
  • Humans
  • Inhibitory Concentration 50
  • Molecular Docking Simulation*

Substances

  • Acridines
  • Cholinesterase Inhibitors
  • Coumarins
  • coumarin
  • Acetylcholinesterase