Abstract
Aim:
To investigate the biotransformation of indomethacin, the first of the newer nonsteroidal anti-inflammatory drugs, by filamentous fungus and to compare the similarities between microbial transformation and mammalian metabolism of indomethacin.
Methods:
Five strains of Cunninghamella (C elegans AS 3.156, C elegans AS 3.2028, C blakesleeana AS 3.153, C blakesleeana AS 3.910 and C echinulata AS 3.2004) were screened for their ability to catalyze the biotransformation of indomethacin. Indomethacin was partially metabolized by five strains of Cunninghamella, and C blakesleeana AS 3.910 was selected for further investigation. Three metabolites produced by C blakesleeana AS 3.910 were isolated using semi-preparative HPLC, and their structures were identified by a combination analysis of LC/MSn and NMR spectra. These three metabolites were separated and quantitatively assayed by liquid chromatography-ion trap mass spectrometry.
Results:
After 120 h of incubation with C blakesleeana AS 3.910, approximately 87.4% of indomethacin was metabolized to three metabolites: O-desmethylindomethacin (DMI, M1, 67.2%), N-deschlorobenzoylindomethacin (DBI, M2, 13.3%) and O-desmethyl-N-deschlorobenzoylindomethacin (DMBI, M3, 6.9%). Three phase I metabolites of indomethacin produced by C blakesleeana AS 3.910 were identical to those obtained in humans.
Conclusion:
C blakesleeana could be a useful tool for generating the mammalian phase I metabolites of indomethacin.
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Project supported by the National High Technology Research and Development Program of China (No 2003AA2Z347C).
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Zhang, P., Lin, Lh., Huang, Hh. et al. Biotransformation of indomethacin by the fungus Cunninghamella blakesleeana. Acta Pharmacol Sin 27, 1097–1102 (2006). https://doi.org/10.1111/j.1745-7254.2006.00350.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00350.x
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