Interactions of safrole and isosafrole and their metabolites with cytochromes P-450.
The structural features which determine interaction of safrole and related methylenedioxyphenyl compounds with cytochromes P-450 or P-448, and determine the induction of these two classes of the cytochrome, have been studied. All methylenedioxyphenyl compounds studied interact with both cytochromes P-450 and P-448 eliciting type I spectral changes and it has been found that the allyl 4-substituent is important in these interactions. Methylenedioxyphenyl compounds with an oxidised allyl 4-substituent exhibited higher affinity for cytochrome P-448 while those possessing an intact allyl or methylvinyl group generally showed higher affinity for cytochrome P-450. Compounds possessing intact allyl and methylenedioxyphenyl groups (safrole, isosafrole and myristicine) were the most potent inducers of cytochromes P-450 and P-448; compounds containing an intact allyl group only (estragole, allybenzene and eugenol methyl ether) or an oxidized allyl group and an intact methylenedioxyphenyl group (epoxysafrole) were inducers of P-448 only.
D000818:Animals; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003580:Cytochromes / Q000378:metabolism; D004149:Dioxoles / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012451:Safrole / Q000378:metabolism* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D003580:Cytochromes; D004149:Dioxoles; D003577:Cytochrome P-450 Enzyme System; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D012451:Safrole; C015959:isosafrole