Metabolic fate of menthofuran in rats. Novel oxidative pathways.
Metabolic fate of menthofuran (II) in rats was investigated. Menthofuran (II) was administered orally (200 mg/kg of the body weight/day) to rats for 3 days. The following metabolites were isolated from the urine of these animals: p-cresol (VI), 5-methyl-2-cyclohexen-1-one (VII), 3-methylcyclohexanone (VIII), 3-methylcyclohexanol (IX), 4-hydroxy-4-methyl-2-cyclohexen-1-one (V), geranic acid (XI), neronic acid (XII), benzoic acid (XIII), and 2-[2'-keto-4'-methylcyclohexyl]propionic acid (X). Incubation of menthofuran (II) with phenobarbital-induced rat liver microsomes in the presence of NADPH and oxygen resulted in the formation of a metabolite tentatively identified as 2-Z-(2'-keto-4'-methylcyclohexylidene)propanal (III; alpha,beta-unsaturated-gamma-keto-aldehyde). The structure assigned was further supported by trapping this metabolite (III) as a cinnoline derivative. Phenobarbital-induced rat liver microsomes also converted 4-methyl-2-cyclohexenone (IV) to 4-hydroxy-4-methyl-2-cyclohexenone (V) and p-cresol (VI) in the presence of NADPH and oxygen. On the basis of both in vivo and in vitro studies, a possible mechanism for the formation of p-cresol from menthofuran has been proposed.
Madyastha
K M
KM
Department of Organic Chemistry, Indian Institute of Science, Bangalore.
Raj
C P
CP
D000818:Animals; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D039821:Monoterpenes; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D013729:Terpenes / Q000378:metabolism* / Q000652:urine
D039821:Monoterpenes; D013729:Terpenes; C054487:menthofuran; D010634:Phenobarbital