Inhibition of epoxide hydrolases and glutathione S-transferases by 2-, 3-, and 4-substituted derivatives of 4'-phenylchalcone and its oxide.
4'-Phenylchalcones, chalcone oxides, and related compounds were synthesized and tested as inhibitors of cytosolic epoxide hydrolase, microsomal epoxide hydrolase, and glutathione S-transferases from mouse and rat liver. Several compounds were more potent inhibitors of the cytosolic epoxide hydrolase than the parent 4'-phenylchalcone oxide while large substituents in the 4- and especially the 2-position caused a reduction in inhibition. The chalcone oxides showed selectivity as inhibitors of the cytosolic epoxide hydrolase acting on trans-stilbene oxide, while chalcones were inhibitors of cytosolic glutathione S-transferase acting on cis-stilbene oxide. Data are consistent with the hypothesis that much of the inhibition of the glutathione S-transferase is caused by the glutathione conjugate of the chalcone.
D000818:Animals; D002599:Chalcone / Q000031:analogs & derivatives / Q000494:pharmacology*; D003600:Cytosol / Q000201:enzymology; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology; D011427:Propiophenones / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D011427:Propiophenones; D002599:Chalcone; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases