@article{APS4045,
author = {Peng Zhang and Li-hong Lin and Hai-hua Huang and Hai-yan Xu and Da-fang Zhong},
title = {Biotransformation of indomethacin by the fungus Cunninghamella blakesleeana },
journal = {Acta Pharmacologica Sinica},
volume = {27},
number = {8},
year = {2016},
keywords = {},
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.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/4045}
}