0090-9556/97/2503-0301-0310$02.00/0
DRUG METABOLISM AND DISPOSITION
Copyright © 1997 by The American Society for Pharmacology and Experimental Therapeutics
Vol. 25, No. 3

Microbial Models of Mammalian Metabolism
Fungal Metabolism of Phenolic and Nonphenolic p-Cymene-Related Drugs and Prodrugs. I. Metabolites of Thymoxamine

Cecile Moussa, Patrick Houziaux, Bernard Danree, and Robert Azerad

Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques (C.M., R.A.), URA 400 CNRS, Université René Descartes; and the Institut de Recherches Chimiques et Biologiques Appliquées (P.H., B.D.)

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--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 -elimination mechanism.