Abstract
Chalcone oxides and several isosteric compounds have been prepared to examine the importance of the α,β-epoxyketone moiety in the inhibition of the hydrolysis of [3H]-trans-stilbene oxide to its meso-diol by mouse liver cytosolic epoxide hydrolase (cEH). Inhibition of microsomal EH and glutathione S-transferase were also examined. For cEH, replacement of the carbonyl by methylidene reduces inhibitor potency by a factor of 44, while replacement of the epoxide ring with a cyclopropyl ring reduces inhibition by a factor of 450. A 2′-hydroxyl also reduces cEH inhibition by 100 times. These observations are consistent with a model of the active site in which the carbonyl is hyhydrogen-bonded to an acidic site presumed to be involved in initiating epoxide hydrolysis. The chalcone oxides thus bind tightly but are not readily turned over as substrates.
Original language | English (US) |
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Pages (from-to) | 11-15 |
Number of pages | 5 |
Journal | Archives of Biochemistry and Biophysics |
Volume | 242 |
Issue number | 1 |
DOIs | |
State | Published - 1985 |
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology