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Epoxy Type Inhibitors of Cholesterol Esterase, Acetylcholinesterase, and Butyrylcholinesterase
Author(s) -
Lin Gialih,
Kao BingHong
Publication year - 2000
Publication title -
journal of the chinese chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.329
H-Index - 45
eISSN - 2192-6549
pISSN - 0009-4536
DOI - 10.1002/jccs.200000053
Subject(s) - butyrylcholinesterase , chemistry , acetylcholinesterase , esterase , enzyme , epoxy , ether , cholinesterase , stereochemistry , substrate (aquarium) , biochemistry , organic chemistry , aché , pharmacology , medicine , oceanography , geology
Epoxy type inhibitors, 3‐ t ‐butylphenyl 3‐1,2‐epoxybutyl ether ( 1 ), 3‐ t ‐butylphenyl 3‐1,2‐epoxyhexyl ether ( 2 ), and 2‐naphthyl 3‐1,2‐epoxyhexyl ether ( 3 ) are synthesized as the active site‐directed inhibitors of cholesterol esterase, acetylcholinesterase, and butyrylcholinesterase. All epoxy compounds are characterized as the time‐independent inhibitors for all three enzymes from the stopped‐time assay. Further, all epoxy compounds are characterized as the competitive inhibitors for all three enzymes from the Lineweaver‐Burk plots. The inhibition constants ( K i ) of cholesterol esterase for compounds 1‐3 are 320 ± 40, 190 ± 20, 130 ± 20 μM, respectively. The K i values of acetylcholinesterase for compounds 1‐3 are 490 ± 20, 141 ± 5, 200 ± 30 μM, respectively. Values of K i of butyrylcholinesterase for compounds 1‐3 are 250 ± 30, 26 ± 4, 120 ± 20 μM, respectively. Compound 2 is the most potent inhibitor for butyrylcholinesterase probably because the compound mimics most the natural substrate, butyrylcholine.