Microbial Models of Mammalian Metabolism

Smith, Robert V.; Rosazza, John P. N.

doi:10.1021/np50025a006

Cited by 71 publications

(31 citation statements)

References 75 publications

(135 reference statements)

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“…The use of microorganisms in the simulation of mammalian metabolic processes provides insight(s) into the mechanisms of action, the toxicity, pharmacological activity (Smith and Rosazza 1974,1975, Smith et al 1977, Davis et al 1985, and the metabolic pathway of drugs (Reighard-and Knapp 1986).…”

Section: Introductionmentioning

confidence: 99%

Microbiological transformation of flavone and isoflavone

Ibrahim

Abul-Hajj

1990

Xenobiotica

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1. Flavone and isoflavone were subjected to microbial transformation studies. Screening with 80 fungal species showed that flavone was transformed by a large number of microorganisms and in higher yields than isoflavone. 2. Large-scale fermentations of flavone followed by isolation and characterization of metabolites using spectroscopic analysis showed the formation of 4'-hydroxyflavone, 3',4'-dihydroxyflavone and two cleavage products identified as o-hydroxyphenyl-hydroxymethyl ketone and 1-(o-hydroxyphenyl)-1,2-ethanediol. However, fermentation of isoflavone gave only 4'-hydroxyisoflavone and 3',4'-dihydroxyisoflavone.

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Section: Introductionmentioning

confidence: 99%

Microbiological transformation of flavone and isoflavone

Ibrahim

Abul-Hajj

1990

Xenobiotica

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“…The synthesis of optically active compounds by using microbial models offers advantages compared with chemical synthesis, because it can be highly enantiomeric and regio-selective under mild conditions [13]. Biotransformation studies with fungi may also provide information for further correlations with enantioselective biotransformation in vivo, for simulating the mammalian metabolism [14,15]. These considerations justify the interest in developing an enantioselective method for the simultaneous determination of DPZ, 6-ODD, and 5-ODD in culture medium to be used in biotransformation studies of DPZ by fungi.…”

Section: Introductionmentioning

confidence: 99%

Chiral HPLC analysis of donepezil, 5-O-desmethyl donepezil and 6-O-desmethyl donepezil in culture medium: application to fungal biotransformation studies

et al. 2012

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An high performance liquid chromatography (HPLC) method for the enantioselective determination of donepezil (DPZ), 5-O-desmethyl donepezil (5-ODD), and 6-O-desmethyl donepezil (6-ODD) in Czapek culture medium to be applied to biotransformation studies with fungi is described for the first time. The HPLC analysis was carried out using a Chiralpak AD-H column with hexane/ethanol/methanol (75:20:5, v/v/v) plus 0.3 % triethylamine as mobile phase and UV detection at 270 nm. Sample preparation was carried out by liquid-liquid extraction using ethyl acetate as extractor solvent. The method was linear over the concentration range of 100-10,000 ng mL(-1) for each enantiomer of DPZ (r ≥ 0.9985) and of 100-5,000 ng mL(-1) for each enantiomer of 5-ODD (r ≥ 0.9977) and 6-ODD (r ≥ 0.9951). Within-day and between-day precision and accuracy evaluated by relative standard deviations and relative errors, respectively, were lower than 15 % for all analytes. The validated method was used to assess DPZ biotransformation by the fungi Beauveria bassiana American Type Culture Collection (ATCC) 7159 and Cunninghamella elegans ATCC 10028B. Using the fungus B. bassiana ATCC 7159, a predominant formation of (R)-5-ODD was observed while for the fungus C. elegans ATCC 10028B, DPZ was biotransformed to (R)-6-ODD with an enantiomeric excess of 100 %.

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“…Traditionally, drug metabolism studies have used model systems to simulate metabolic pathways of drugs in humans and animals. Microorganisms such as bacteria and fungi have been used as in vitro models for the simulation of mammalian drug metabolism, and successful applications have been reported in the literature [1][2][3][4][5][6]. Interestingly, some fungi were found to possess cytochrome p450 enzyme system [7] and oxidizing organic compounds in the same way as mammalian hepatic cytochrome p-450.…”

Section: Introductionmentioning

confidence: 99%

Biotransformation of Celecoxib Using Microbial Cultures

Srisailam

Veeresham

2009

Appl Biochem Biotechnol

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Microbial transformation studies can be used as models to simulate mammalian drug metabolism. In the present investigation, biotransformation of celecoxib was studied in microbial cultures. Bacterial, fungal, and yeast cultures were employed in the present study to elucidate the metabolism of celecoxib. The results indicate that a number of microorganisms metabolized celecoxib to various levels to yield eight metabolites, which were identified by high-performance liquid chromatography diode array detection and liquid chromatography tandem mass spectrometry analyses. HPLC analysis of biotransformed products indicated that majority of the metabolites are more polar than the substrate celecoxib. The major metabolite was found to be hydroxymethyl metabolite of celecoxib, while the remaining metabolites were produced by carboxylation, methylation, acetylation, or combination of these reactions. The methyl hydroxylation and further conversion to carboxylic acid was known to occur in metabolism by mammals. The results further support the use of microorganisms for simulating mammalian metabolism of drugs.

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Microbial Models of Mammalian Metabolism

Cited by 71 publications

References 75 publications

Microbiological transformation of flavone and isoflavone

Microbiological transformation of flavone and isoflavone

Chiral HPLC analysis of donepezil, 5-O-desmethyl donepezil and 6-O-desmethyl donepezil in culture medium: application to fungal biotransformation studies

Biotransformation of Celecoxib Using Microbial Cultures

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