Biotransformation of Flurbiprofen by Cunninghamella Species

被引:36
作者
Amadio, Jessica [1 ]
Gordon, Katherine [1 ]
Murphy, Cormac D. [1 ]
机构
[1] Natl Univ Ireland Univ Coll Dublin, Sch Biomol & Biomed Sci, Ctr Synth & Chem Biol, Dublin 4, Ireland
关键词
MAMMALIAN METABOLISM; CYTOCHROME-P450; 2C9; MICROBIAL MODELS; DRUG-METABOLISM; TRANSFORMATION; ELEGANS; 4'-HYDROXYLATION; CHROMATOGRAPHY; URINE;
D O I
10.1128/AEM.01027-10
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The biotransformation of the fluorinated anti-inflammatory drug flurbiprofen was investigated in Cunninghamella spp. Mono- and dihydroxylated metabolites were detected using gas chromatography-mass spectrometry and fluorine-19 nuclear magnetic resonance spectroscopy, and the major metabolite 4'-hydroxyflurbiprofen was isolated by preparative high-pressure liquid chromatography (HPLC). Cunninghamella elegans DSM 1908 and C. blakesleeana DSM 1906 also produced a phase II (conjugated) metabolite, which was identified as the sulfated drug via deconjugation experiments.
引用
收藏
页码:6299 / 6303
页数:5
相关论文
共 21 条
[1]   SIMULTANEOUS DETERMINATION OF FLURBIPROFEN AND ITS MAJOR METABOLITE IN PHYSIOLOGICAL FLUIDS USING LIQUID-CHROMATOGRAPHY WITH FLUORESCENCE DETECTION [J].
ADAMS, WJ ;
BOTHWELL, BE ;
BOTHWELL, WM ;
VANGIESSEN, GJ ;
KAISER, DG .
ANALYTICAL CHEMISTRY, 1987, 59 (11) :1504-1509
[2]   Biotransformation of fluorobiphenyl by Cunninghamella elegans [J].
Amadio, Jessica ;
Murphy, Cormac D. .
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, 2010, 86 (01) :345-351
[3]   Cunninghamella - A microbial model for drug metabolism studies - A review [J].
Asha, Sepuri ;
Vidyavathi, Maravajhala .
BIOTECHNOLOGY ADVANCES, 2009, 27 (01) :16-29
[4]  
Azerad R, 1999, Adv Biochem Eng Biotechnol, V63, P169
[5]  
CANNELL RJP, 1995, DRUG METAB DISPOS, V23, P724
[6]   Flurbiprofen, a unique non-steroidal anti-inflammatory drug with antimicrobial activity against Trichophyton, Microsporum and Epidermophyton species [J].
Chowdhury, B ;
Adak, M ;
Bose, SK .
LETTERS IN APPLIED MICROBIOLOGY, 2003, 37 (02) :158-161
[7]   The potential of 19F NMR spectroscopy for rapid screening of cell cultures for models of mammalian drug metabolism [J].
Corcoran, O ;
Lindon, JC ;
Hall, R ;
Ismail, IM ;
Nicholson, JK .
ANALYST, 2001, 126 (12) :2103-2106
[8]   Microbial models of mammalian metabolism: uses and misuses (clarification of some misconceptions) [J].
Jezequel, SG .
JOURNAL OF MOLECULAR CATALYSIS B-ENZYMATIC, 1998, 5 (1-4) :371-377
[9]   HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ANALYSIS OF THE ENANTIOMERS OF FLURBIPROFEN AND ITS METABOLITES IN PLASMA AND URINE [J].
KNADLER, MP ;
HALL, SD .
JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS, 1989, 494 :173-182
[10]   Transformation of amoxapine by Cunninghamella elegans [J].
Moody, JD ;
Zhang, DL ;
Heinze, TM ;
Cerniglia, CE .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2000, 66 (08) :3646-3649