Formation of conjugates from ciprofloxacin and norfloxacin in cultures of Trichoderma viride

Abstract

The formation of conjugates from two antibacterial fluoroquinolone drugs, ciprofloxacin and norfloxacin, was observed in cultures of Trichoderma viride that had been grown in sucrose-peptone broth and extracted 16 d after dosing with the drugs. Both conjugates were purified by high-performance liquid chromatography and found to be optically active. They were identified by mass and proton nuclear magnetic resonance spectra as 4-hydroxy-3-oxo-4-vinylcyclopent-1-enyl ciprofloxacin and 4-hydroxy-3-oxo-4-vinylcyclopent-1-enyl norfloxacin. The transformation of veterinary fluoroquinolones in the presence of fungi may have ecological significance.

• biotransformation
• fluoroquinolones

We thank C. E. Cerniglia and E. B. Hansen, Jr., for their useful suggestions, P. P. Fu and L. S. von Tungeln for circular dichroism spectroscopy, S. N. Lekomtseva for the identification of T. viride, and J. V. Pothuluri for comments on the manuscript. We also thank Bayer Corp. for kindly providing us with the ciprofloxacin.

This work was supported in part by an appointment to the Postgraduate Research Program at the National Center for Toxicological Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration.