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.