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Biotransformation of indomethacin by the fungus Cunninghamella blakesleeana.
Acta Pharmacol Sin. 2006 Aug; 27(8):1097-102.AP

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/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.

Authors+Show Affiliations

Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, Shenyang 110016, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16867265

Citation

Zhang, Peng, et al. "Biotransformation of Indomethacin By the Fungus Cunninghamella Blakesleeana." Acta Pharmacologica Sinica, vol. 27, no. 8, 2006, pp. 1097-102.
Zhang P, Lin LH, Huang HH, et al. Biotransformation of indomethacin by the fungus Cunninghamella blakesleeana. Acta Pharmacol Sin. 2006;27(8):1097-102.
Zhang, P., Lin, L. H., Huang, H. H., Xu, H. Y., & Zhong, D. F. (2006). Biotransformation of indomethacin by the fungus Cunninghamella blakesleeana. Acta Pharmacologica Sinica, 27(8), 1097-102.
Zhang P, et al. Biotransformation of Indomethacin By the Fungus Cunninghamella Blakesleeana. Acta Pharmacol Sin. 2006;27(8):1097-102. PubMed PMID: 16867265.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Biotransformation of indomethacin by the fungus Cunninghamella blakesleeana. AU - Zhang,Peng, AU - Lin,Li-Hong, AU - Huang,Hai-Hua, AU - Xu,Hai-Yan, AU - Zhong,Da-Fang, PY - 2006/7/27/pubmed PY - 2007/9/8/medline PY - 2006/7/27/entrez SP - 1097 EP - 102 JF - Acta pharmacologica Sinica JO - Acta Pharmacol. Sin. VL - 27 IS - 8 N2 - 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. SN - 1671-4083 UR - https://www.unboundmedicine.com/medline/citation/16867265/Biotransformation_of_indomethacin_by_the_fungus_Cunninghamella_blakesleeana_ L2 - http://dx.doi.org/10.1111/j.1745-7254.2006.00350.x DB - PRIME DP - Unbound Medicine ER -