Open AccessBiotransformation of indomethacin by the fungus Cunninghamella blakesleeana 1
Author(s) -
ZHANG Peng,
LIN Lihong,
HUANG Haihua,
XU Haiyan,
ZHONG Dafang
Publication year - 2006
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2006.00350.x
Subject(s) - biotransformation , fungus , traditional medicine , chemistry , microbiology and biotechnology , medicine , biology , botany , organic chemistry , enzyme
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/MS n 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.