Microbial Models of Mammalian Metabolism: Fungal Metabolism of Phenolic and Nonphenolicp-Cymene-Related Drugs and Prodrugs. II. Metabolites of Nonphenolic Derivatives

Cecile Moussa; Patrick Houziaux; Bernard Danree; Robert Azerad

Fungal Metabolism of Phenolic and Nonphenolicp-Cymene-Related Drugs and Prodrugs. II. Metabolites of Nonphenolic Derivatives

Abstract

A cymene-derived drug, 3-[4′-(o-ethoxyphenyl)piperazin-1′-yl]ethyloxy-p-cymene (B1178), is not significantly metabolized by fungal microorganisms. On the contrary, one of its metabolites in rat, 3-(piperazin-1′-yl)ethoxy-p-cymene (B1071), is quantitatively converted by Cunninghamella echinulata NRRL 3655 into two hydroxylated products: the corresponding phenol derivative and a benzylic alcohol derivative. Other strains, such asBeauveria bassiana ATCC 7159 and Mortierella isabellina MMP 108, produce exclusively an N-acetyl derivative in high yield. Results obtained are discussed on the grounds of relative hydrophobicity of substrates vs. fungi metabolism and detoxification capabilities.

Footnotes

Send reprint requests to: Dr. Robert Azerad, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, URA 400 CNRS, Université René Descartes, 45 rue des Saints-Pères, 75270-Paris Cedex 06, France.
This study was supported by the Institut de Recherches Chimiques et Biologiques Appliquées (Vicq, France), Laboratoires Fournier (Dijon, France), and partially by a European Communities Programme “Human Capital and Mobility: Biooxygenations” (Contract ERBCHRXCT930259). This work was completed by C. Moussa in partial fulfillment of her Doctorate of Science degree. A preliminary part of this work was realized with the efficient participation of M. Da Eira.
Abbreviations used are::
B1178
3-[4′-(o-ethoxyphenyl)piperazin-1′-yl]ethyloxy-p-cymene, monohydrochloride
B1071
3-(piperazin-1′-yl)ethoxy-p-cymene
- Received July 2, 1996.
- Accepted December 10, 1996.