Synthesis and study of thiocarbonate derivatives of choline as potential inhibitors of acetylcholinesterase

J Med Chem. 1997 Sep 12;40(19):3009-13. doi: 10.1021/jm970141k.


Fourteen alkyl and aryl thiocarbonate derivatives of choline were synthesized and studied as potential inhibitors of acetylcholinesterase (AChE). Twelve of the compounds inhibited AChEs derived from calf forebrain, human red blood cells, and octopus brain ranging from low to moderately high inhibition potency. The concentration of each inhibitory compound giving 50% inhibition of enzyme activity (IC50 values, which ranged from 1 x 10(-2) to 8 x 10(-7) M) was determined and is reported; inhibitor constants (Ki values) for the most inhibitory compounds, (1-pentylthiocarbonyl)choline chloride and (1-heptylthiocarbonyl)choline chloride, were calculated from kinetic data and are also reported. The inhibitors are competitive with substrate, and they are not hydrolyzed by the AChE activities. Certain of these new compounds may provide direction for the development of new drugs that have anticholinesterase activity and may be used for the treatment of Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Animals
  • Carbonates / chemical synthesis*
  • Carbonates / chemistry
  • Carbonates / pharmacology
  • Cattle
  • Choline / analogs & derivatives*
  • Choline / chemical synthesis*
  • Choline / chemistry
  • Choline / pharmacology
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology
  • Erythrocytes / enzymology
  • Humans
  • Indicators and Reagents
  • Kinetics
  • Octopodiformes
  • Prosencephalon / enzymology
  • Structure-Activity Relationship


  • Carbonates
  • Cholinesterase Inhibitors
  • Indicators and Reagents
  • Acetylcholinesterase
  • Choline