Anticholinesterase activity of potential therapeutic 5-(1,3,3-trimethylindolinyl) carbamates. |
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Authors: | C N Lieske R T Gepp J H Clark H G Meyer P Blumbergs C C Tseng |
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Institution: | U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010. |
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Abstract: | Six N-alkyl and N-aryl 5-(1,3,3-trimethylindolinyl) carbamates were synthesized and studied for their structure-activity relationships in inhibiting eel acetylcholinesterase (AChE). The carbamates were 5-(1,3,3-trimethylindolinyl)N,N-dimethylcarbamate (Cui Xing Ning) (I), 5-(1,3,3-trimethylindolinyl)N,N-diethylcarbamate (IV), 5-(1,3,3-trimethylindolinyl)N-ethylcarbamate (III), 5-(1,3,3-trimethylindolinyl)N,N-diethylcarbamate (IV), 5-(1,3,3-trimethylindolinyl)N-heptylcarbamate (V), and 5-(1,3,3-trimethylindolinyl)N-(3-chlorophenyl)carbamate (VI). The inhibition studies were carried out at 25.0 degrees C at pH 7.60. The rank order of the ki values for eel AChE inhibition is II > V > I > III > VI > IV. Compound II has a greater affinity for the enzyme than any irreversible inhibitor cited in the literature (Kd = 7.14 x 10(-8) M). Our findings should aid in the application of these carbamates (1) for counteracting the cholinergic problems associated with various diseases, and (2) for developing potential pretreatment compounds for organophosphate poisoning. |
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