Epoxy type inhibitors of cholesterol esterase, acetylcholinesterase, and butyrylcholinesterase

Epoxy type inhibitors, 3-t-butylphenyl 3-1,2-epoxybutyl ether (1), 3-t-buty lphenyl 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 es terase, acetylcholinesterase, and butyrylcholinesterase. All epoxy compound s are characterized as the time-independent inhibitors for all three enzyme s from the stopped-time assay. Further, all epoxy compounds are characteriz ed as the competitive inhibitors for all three enzymes from the Lineweavcr- Burk plots. The inhibition constants (K-i) of cholesterol esterase for comp ounds 1-3 are 320 +/- 40, 190 +/- 20, 130 +/- 20 mu M, respectively. The K- i values of acetylcholinesterase for compounds 1-3 are 490 +/- 20, 141 +/- 5, 200 +/- 30 mu M, respectively. Values of K-i of butyrylcholinesterase fo r compounds 1-3 are 250 +/- 30, 26 +/- 4, 120 +/- 20 mu M, respectively. Co mpound 2 is the most potent inhibitor for butyrylcholinesterase probably be cause the compound mimics most the natural substrate, butyrylcholine.