Microbial transformation of naproxen by Cunninghamella species.
OBJECTIVE
The metabolites of naproxen produced by Cunninghamella species were isolated and identified, and further to compare the similarities between microbial transformation and mammalian metabolism.


METHODS
Naproxen was transformed by three strains of Cunninghammella species (Cunninghamella blakeslesna AS 3.153, Cunninghamella echinulata AS 3.2004, and Cunninghamella elegans AS 3.156). The metabolites of naproxen were separated and assayed by liquid chromatography-mass spectrometry method. Semi-preparative HPLC was used to isolate the major metabolite, and the structure was identified by nuclear magnetic resonance (NMR) and mass spectrometry.


RESULTS
Naproxen was transformed into 2 metabolites, desmethylnaproxen and desmethylnaproxen-6-O-sulfate, both were the known mammalian metabolites. The conjugated metabolite was newly detected in microbial transformation samples.


CONCLUSIONS
The microbial transformation of naproxen has some similarities with the metabolism of naproxen in mammals. The fungi belonging to Cunninghamella species could be used as complementary in vitro models for drug metabolism to predict and produce the metabolites of drugs in mammals.
Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, Shenyang 110016, China. zhongdf@china.com
Da-Fang
DF
Zhong
Lu
L
Sun
Lei
L
Liu
Hai-Hua
HH
Huang
D001711:Biotransformation; D020093:Cunninghamella / Q000145:classification / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism*; D009288:Naproxen / Q000031:analogs & derivatives* / Q000378:metabolism*
D016861:Cyclooxygenase Inhibitors; D009288:Naproxen; C034451:desmethylnaproxen