Repurposing N,N'-bis-(arylamidino)-1,4-piperazinedicarboxamidines: An unexpected class of potent inhibitors of cholinesterases

Eur J Med Chem. 2017 Jan 5:125:430-434. doi: 10.1016/j.ejmech.2016.09.051. Epub 2016 Sep 19.

Abstract

Drug repurposing (=drug repositioning) is an effective way to cut costs for the development of new therapeutics and to reduce the time-to-market time-span. Following this concept a small library of compounds was screened for their ability to act as inhibitors of acetyl- and butyrylcholinesterase. Picloxydine, an established antiseptic, was shown to be an inhibitor for both enzymes. Systematic variation of the aryl substituents led to analogs possessing almost the same good properties as gold standard galantamine hydrobromide.

Keywords: Acetylcholinesterase; Bisbiguanides; Butyrylcholinesterase; Picloxydine.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Anti-Infective Agents, Local / chemistry*
  • Anti-Infective Agents, Local / pharmacology*
  • Butyrylcholinesterase / metabolism
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / pharmacology*
  • Drug Repositioning*
  • Humans
  • Molecular Docking Simulation
  • Piperazines / chemistry*
  • Piperazines / pharmacology*

Substances

  • Anti-Infective Agents, Local
  • Cholinesterase Inhibitors
  • Piperazines
  • picloxydine
  • Acetylcholinesterase
  • Butyrylcholinesterase