Hydrolysis of the 2',3'-allylic epoxides of allylbenzene, estragole, eugenol, and safrole by both microsomal and cytosolic epoxide hydrolases.
2',3'-Allylic epoxide derivatives of allylbenzene and its analogs estragole, eugenol, and safrole were synthesized, and their enzymatic conversion to dihydrodiols by cytosolic and microsomal epoxide hydrolases was examined. All four epoxides were good substrates for both epoxide hydrolases, with Michaelis constants in the low micromolar range. Two putatively selective inhibitors of cytosolic and microsomal epoxide hydrolases, trichloropropylene oxide and nordihydroguaiaretic acid, were used to inhibit the hydrolysis of these allylic epoxides. Minimal selectivity toward either hydrolase was seen with either inhibitor, suggesting that the "selectivity" of these inhibitors is highly substrate-dependent. The susceptibilities of these epoxides to rapid hydrolysis by both epoxide hydrolases may explain their low genotoxic potencies in vivo.
Luo
G
G
Department of Pharmacology, University of Illinois College of Medicine, Chicago 60612.
Qato
M K
MK
Guenthner
T M
TM
D000081248:Allylbenzene Derivatives; D000840:Anisoles / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D003600:Cytosol / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000378:metabolism*; D005054:Eugenol / Q000737:chemistry / Q000378:metabolism; D006139:Guaiacol / Q000031:analogs & derivatives / Q000494:pharmacology; D006868:Hydrolysis; D017705:Lignans; D008861:Microsomes / Q000378:metabolism; D012451:Safrole / Q000737:chemistry / Q000378:metabolism; D014239:Trichloroepoxypropane / Q000494:pharmacology
D000081248:Allylbenzene Derivatives; D000840:Anisoles; D004852:Epoxy Compounds; D017705:Lignans; D014239:Trichloroepoxypropane; C015816:dihydroguaiaretic acid; D005054:Eugenol; D006139:Guaiacol; C007633:estragole; D004851:Epoxide Hydrolases; D012451:Safrole