title: Microbial models of mammalian metabolism. Fungal metabolism of phenolic and nonphenolic p-cymene-related drugs and prodrugs. I. Metabolites of thymoxamine.
abstract: This study was undertaken to validate the use of microbial biotransformation systems for drug metabolism studies. Thymoxamine 1 was rapidly hydrolyzed to desacetylthymoxamine (DAT) 2 by numerous fungi. Other known animal metabolites, such as N-desmethyl-desacetylthymoxamine 3 and desacetylthymoxamine-O-sulfate 6, were produced from DAT by Mucor rouxii and Mortierella isabellina. DAT-N-oxide 5, a putative animal microsomal metabolite, was also produced by M. isabellina, in addition, a few strains (such as Actinomucor elegans, Mucor hiemalis, and Mucor janssenii) produced a glycosylated metabolite that was identified by high-resolution 1H- and 13C-NMR, MS, and enzymatic hydrolysis as the corresponding [4-(2-dimethylaminoethoxy)-5-isopropyl-2-methyl-phenyl]-1-beta-D- glucopyranoside 7. A similar glucosylation reaction was observed when thymohydroquinone 10 was incubated with A. elegans. Several strains were able to produce transiently thymohydroquinone from DAT-N-oxide 5, possibly through a beta-elimination mechanism.
authors.affiliation: Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, URA 400 CNRS, Université René Descartes, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Moussa
authors.forename: P
authors.initials: P
authors.lastname: Houziaux
authors.forename: B
authors.initials: B
authors.lastname: Danree
authors.forename: R
authors.initials: R
authors.lastname: Azerad
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000378:metabolism* / Q000493:pharmacokinetics; D001711:Biotransformation; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005658:Fungi / Q000378:metabolism*; D013948:Moxisylyte / Q000378:metabolism* / Q000493:pharmacokinetics; D011355:Prodrugs / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D000317:Adrenergic alpha-Antagonists; D011355:Prodrugs; D013948:Moxisylyte