SYNTHESIS AND STUDY OF THIOCARBONATE DERIVATIVES OF CHOLINE AS POTENTIAL OF ACETYLCHOLINESTERASE

Fourteen alkyl and aryl thiocarbonate derivatives of choline were synt hesized and studied as potential inhibitors of acetylcholinesterase (A ChE). Twelve of the compounds inhibited AChEs derived from calf forebr ain, human red blood cells, and octopus brain ranging from low to mode rately high inhibition potency. The concentration of each inhibitory c ompound giving 50% inhibition of enzyme activity (IC50 values, which r anged from 1 x 10(-2) to 8 x 10(-7) M) was determined and is reported; inhibitor constants (K-i values) for the most inhibitory compounds, ( 1-pentylthiocarbonyl)choline chloride and (1-heptylthiocarbonyl)cholin e chloride, were calculated from kinetic data and are also reported. T he: inhibitors are competitive with substrate, and they are not hydrol yzed by the AChE activities. Certain of these new compounds may provid e direction for the development of new drugs that have anticholinester ase activity and may be used for the treatment of Alzheimer's disease.