Microbial models of mammalian metabolism. Fungal metabolism of phenolic and nonphenolic p-cymene-related drugs and prodrugs. II. Metabolites of nonphenolic derivatives.
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 as Beauveria 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.
Moussa
C
C
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, URA 400 CNRS, Université René Descartes, Paris, France.
Houziaux
P
P
Danree
B
B
Azerad
R
R
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism* / Q000493:pharmacokinetics; D001711:Biotransformation; D000081007:Cymenes; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005658:Fungi / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D039821:Monoterpenes; D010879:Piperazines / Q000378:metabolism* / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000378:metabolism* / Q000493:pharmacokinetics
D000317:Adrenergic alpha-Antagonists; C105927:B 1178; D000081007:Cymenes; D039821:Monoterpenes; D010879:Piperazines; D011355:Prodrugs