Design, synthesis and bioactivity of novel phthalimide derivatives as acetylcholinesterase inhibitors

Bioorg Med Chem Lett. 2016 May 1;26(9):2380-2. doi: 10.1016/j.bmcl.2015.07.052. Epub 2015 Jul 26.

Abstract

A series of novel phthalimide derivatives related to benzylpiperazine were synthesized and evaluated as cholinesterase inhibitors. The results showed that all compounds were able to inhibit acetylcholinesterase (AChE), with two of them dramatically inhibiting butyrylcholinesterase (BuChE). Most compounds exhibited potent anti-AChE activity in the range of nM concentrations. In particular, compounds 7aIII and 10a showed the most potent activity with the IC50 values of 18.44 nM and 13.58 nM, respectively. To understand the excellent activity of these compounds, the structure-activity relationship was further examined. The protein-ligand docking study demonstrated that the target compounds have special binding modes and these results are in agreement with the kinetic study.

Keywords: Acetylcholinesterase inhibitor; Molecular docking; Phthalimide derivatives; Structure–activity relationship; Substructure combination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / drug effects*
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Humans
  • Phthalimides / chemical synthesis*
  • Phthalimides / chemistry
  • Phthalimides / pharmacology*

Substances

  • Cholinesterase Inhibitors
  • Phthalimides
  • Acetylcholinesterase