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Biotransformation of pantoprazole by the fungus Cunninghamella blakesleeana.
Xenobiotica. 2005 May; 35(5):467-77.X

Abstract

To investigate the biotransformation of pantoprazole, a proton-pump inhibitor, by filamentous fungus and further to compare the similarities between microbial transformation and mammalian metabolism of pantoprazole, four strains of Cunninghamella (C. blakesleeana AS 3.153, C. echinulata AS 3.2004, C. elegans AS 3.156, and AS 3.2028) were screened for the ability to catalyze the biotransformation of pantoprazole. Pantoprazole was partially metabolized by four strains of Cunninghamella, and C. blakesleeana AS 3.153 was selected for further investigation. Three metabolites produced by C. blakesleeana AS 3.153 were isolated using semi-preparative HPLC, and their structures were identified by a combination analysis of LC/MS(n) and NMR spectra. Two further metabolites were confirmed with the aid of synthetic reference compounds. The structure of a glucoside was tentatively assigned by its chromatographic behavior and mass spectroscopic data. These six metabolites were separated and quantitatively assayed by liquid chromatography-ion trap mass spectrometry. After 96h of incubation with C. blakesleeana AS 3.153, approximately 92.5% of pantoprazole was metabolized to six metabolites: pantoprazole sulfone (M1, 1.7%), pantoprazole thioether (M2, 12.4%), 6-hydroxy-pantoprazole thioether (M3, 1.3%), 4'-O-demethyl-pantoprazole thioether (M4, 48.1%), pantoprazole thioether-1-N-beta-glucoside (M5, 20.6%), and a glucoside conjugate of pantoprazole thioether (M6, 8.4%). Among them, M5 and M6 are novel metabolites. Four phase I metabolites of pantoprazole produced by C. blakesleeana were essentially similar to those obtained in mammals. C. blakesleeana could be a useful tool for generating the mammalian phase I metabolites of pantoprazole.

Authors+Show Affiliations

Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16012078

Citation

Xie, Z Y., et al. "Biotransformation of Pantoprazole By the Fungus Cunninghamella Blakesleeana." Xenobiotica; the Fate of Foreign Compounds in Biological Systems, vol. 35, no. 5, 2005, pp. 467-77.
Xie ZY, Huang HH, Zhong DF. Biotransformation of pantoprazole by the fungus Cunninghamella blakesleeana. Xenobiotica. 2005;35(5):467-77.
Xie, Z. Y., Huang, H. H., & Zhong, D. F. (2005). Biotransformation of pantoprazole by the fungus Cunninghamella blakesleeana. Xenobiotica; the Fate of Foreign Compounds in Biological Systems, 35(5), 467-77.
Xie ZY, Huang HH, Zhong DF. Biotransformation of Pantoprazole By the Fungus Cunninghamella Blakesleeana. Xenobiotica. 2005;35(5):467-77. PubMed PMID: 16012078.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Biotransformation of pantoprazole by the fungus Cunninghamella blakesleeana. AU - Xie,Z Y, AU - Huang,H H, AU - Zhong,D F, PY - 2005/7/14/pubmed PY - 2005/9/22/medline PY - 2005/7/14/entrez SP - 467 EP - 77 JF - Xenobiotica; the fate of foreign compounds in biological systems JO - Xenobiotica VL - 35 IS - 5 N2 - To investigate the biotransformation of pantoprazole, a proton-pump inhibitor, by filamentous fungus and further to compare the similarities between microbial transformation and mammalian metabolism of pantoprazole, four strains of Cunninghamella (C. blakesleeana AS 3.153, C. echinulata AS 3.2004, C. elegans AS 3.156, and AS 3.2028) were screened for the ability to catalyze the biotransformation of pantoprazole. Pantoprazole was partially metabolized by four strains of Cunninghamella, and C. blakesleeana AS 3.153 was selected for further investigation. Three metabolites produced by C. blakesleeana AS 3.153 were isolated using semi-preparative HPLC, and their structures were identified by a combination analysis of LC/MS(n) and NMR spectra. Two further metabolites were confirmed with the aid of synthetic reference compounds. The structure of a glucoside was tentatively assigned by its chromatographic behavior and mass spectroscopic data. These six metabolites were separated and quantitatively assayed by liquid chromatography-ion trap mass spectrometry. After 96h of incubation with C. blakesleeana AS 3.153, approximately 92.5% of pantoprazole was metabolized to six metabolites: pantoprazole sulfone (M1, 1.7%), pantoprazole thioether (M2, 12.4%), 6-hydroxy-pantoprazole thioether (M3, 1.3%), 4'-O-demethyl-pantoprazole thioether (M4, 48.1%), pantoprazole thioether-1-N-beta-glucoside (M5, 20.6%), and a glucoside conjugate of pantoprazole thioether (M6, 8.4%). Among them, M5 and M6 are novel metabolites. Four phase I metabolites of pantoprazole produced by C. blakesleeana were essentially similar to those obtained in mammals. C. blakesleeana could be a useful tool for generating the mammalian phase I metabolites of pantoprazole. SN - 0049-8254 UR - https://www.unboundmedicine.com/medline/citation/16012078/Biotransformation_of_pantoprazole_by_the_fungus_Cunninghamella_blakesleeana_ L2 - http://www.tandfonline.com/doi/full/10.1080/00498250500111414 DB - PRIME DP - Unbound Medicine ER -