Biotransformation of indomethacin by the fungus Cunninghamella blakesleeana1

Zhang, Peng; Lin, Li-hong; Huang, Haihua; Xu, Huibi; Zhong, Dafang

doi:10.1111/j.1745-7254.2006.00350.x

Cited by 19 publications

(14 citation statements)

References 9 publications

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“…5) (Bright et al 2011). Zhang et al (2006) examined the biotransformation of indomethacin by Cunninghamella blakesleeana AS 3.910. The drug was partially metabolized (87.41 %) to three metabolites: O-desmethylindomethacin, Ndeschlorobenzoylindomethacin and O-desmethyl-Ndeschlorobenzoylindomethacin.…”

Section: Mefenamic Acid Indomethacin and Flurbiprofen Biodegradationmentioning

confidence: 99%

“…The drug was partially metabolized (87.41 %) to three metabolites: O-desmethylindomethacin, Ndeschlorobenzoylindomethacin and O-desmethyl-Ndeschlorobenzoylindomethacin. Transformation of the drug was also carried out by C. elegans AS 3.156 (38.76 %), C. elegans AS 3.2028 (69.29 %), C. blakesleeana AS 3.153 (51.90 %) and C. echinulata AS 3.2004 (39.52 %), but metabolites of indomethacin were not identified (Zhang et al 2006) (Fig. 6).…”

Section: Mefenamic Acid Indomethacin and Flurbiprofen Biodegradationmentioning

confidence: 99%

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Biodegradation and biotransformation of polycyclic non-steroidal anti-inflammatory drugs

Domaradzka

Guzik

Wojcieszyńska

2015

Rev Environ Sci Biotechnol

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In recent years the increased use of polycyclic non-steroidal anti-inflammatory drugs has resulted in their presence in the environment. This in turn may cause potential negative effects on living organisms. While the biotransformation mechanisms of polycyclic non-steroidal anti-inflammatory drugs in the human body and in other mammals have been extensively studied, degradation of these drugs by microorganisms has seldom been investigated and is largely unknown. Biotransformation/biodegradation of polycyclic nonsteroidal anti-inflammatory drugs is caused by fungal microorganisms, mainly white-rot fungi, and a few strains of bacteria. However, hitherto only complete degradation of olsazine was described. The first step of the transformation is most often hydroxylation catalyzed by cytochrom P-450 monooxygenases, or oxygenation by laccases and three peroxidases: lignin peroxidase, manganese-dependent peroxidase and versatile peroxidase manganese-dependent peroxidase. The aim of this work is to summarize the knowledge about the biotransformation and/or biodegradation of polycyclic non-steroidal anti-inflammatory drugs and to present their biotransformation pathways.

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Section: Mefenamic Acid Indomethacin and Flurbiprofen Biodegradationmentioning

confidence: 99%

Section: Mefenamic Acid Indomethacin and Flurbiprofen Biodegradationmentioning

confidence: 99%

Biodegradation and biotransformation of polycyclic non-steroidal anti-inflammatory drugs

Domaradzka

Guzik

Wojcieszyńska

2015

Rev Environ Sci Biotechnol

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“…Cultures of 5 strains of Cunninghamella were chosen for this investigation, because such fungi have the ability to metabolize drugs, including verapamil [9] , pantoprazole [10] , and indomethacin [11] , in a similar manner to mammals. The main focus of the current study was to investigate the metabolic fate of metoprolol in cultures of the 5 strains of Cunninghamella and demonstrate parallels of the metabolism of metoprolol in mammalian and in microbial systems.…”

Section: Introductionmentioning

confidence: 99%

Biotransformation of metoprolol by the fungus Cunninghamella blakesleeana

Huang

Chen

et al. 2007

Acta Pharmacologica Sinica

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Aim: To investigate the biotransformation of metoprolol, a β1‐cardioselective adrenoceptor antagonist, by filamentous fungus, and to compare the parallels between microbial transformation and mammalian metabolism. Methods: Five strains of Cunninghamella (Celegans AS 3.156, Celegans AS 3.2028, C echinulata AS 3.2004, C blakesleeana AS 3.153 and AS 3.910) were screened for the ability to transform metoprolol. The metabolites of metoprolol produced by C blakesleeana AS 3.153 were separated and assayed by liquid chromatography‐tandem mass spectrometry (LC/MSn). The major metabolites were isolated by semipreparative HPLC and the structures were identified by a combination of LC/MSn and nuclear magnetic resonance analysis. Results: Metoprolol was transformed to 7 metabolites; 2 were identified as new metabolites and 5 were known metabolites in mammals. Conclusion: The microbial transformation of metoprolol was similar to the metabolism in mammals. The fungi belonging to Cunninghamella species could be used as complementary models for predicting in vivo metabolism and producing quantities of metabolite references for drugs like metoprolol.

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“…Electron ionization (EI-MS) and high resolution electron ionization mass spectra (HREI-MS) were recorded on JEOL JMS600H mass spectrometer (JEOL, Japan). 1 H-, 13 C-and 2D-NMR spectra were recorded on Bruker Avance spectrometers (Bruker, Switzerland) in CD 3 OD. X-Ray diffraction data of the compound 6 was recorded on Bruker SMART APEX II single-crystal X-ray diffractometer (Germany).…”

Section: Methodsmentioning

confidence: 99%

“…[1][2][3][4][5][6] Biotransformation reactions can be achieved by a variety of agents, such as enzymes, animals and plant cell cultures, and microorganisms; however, microorganisms are most effectively used for this purpose. Microbial enzyme systems can be used for reduction, oxidation, hydroxylation, and Michael addition.…”

Section: Introductionmentioning

confidence: 99%

Microbial transformation of mestanolone byMacrophomina phaseolinaandCunninghamella blakesleeanaand anticancer activities of the transformed products

et al. 2018

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The microbial transformation of anabolic androgenic steroid mestanolone (1) with Macrophomina phaseolina and Cunninghamella blakesleeana has afforded seven metabolites. The structures of these metabolites were characterized as 17b-hydroxy-17a-methyl-5a-androsta-1-ene-3,11-dione (2), 14a,17b-dihydroxy-17a-methyl-5a-androstan-3,11-dione (3), 17b-hydroxy-17a-methyl-5a-androstan-1,14-diene-3,11-dione (4), 17b-hydroxy-17a-methyl-5a-androstan-3,11-dione (5), 11b,17b-dihydroxy-17a-methyl-5a-androstan-1-ene-3-one (6), 9a,11b,17b-trihydroxy-17a-methyl-5a-androstan-3-one (7), and 1b,11a,17b-trihydroxy-17a-methyl-5a-androstan-3-one (8). All the metabolites, except 5 and 6, were identified as new compounds. Substrate 1 (IC 50 ¼ 27.6 AE 1.1 mM), and its metabolites 2 (IC 50 ¼ 19.2 AE 2.9 mM) and 6 (IC 50 ¼ 12.8 AE 0.6 mM) exhibited moderate cytotoxicity against the HeLa cancer cell line (human cervical carcinoma). All metabolites were noncytotoxic to 3T3 (mouse fibroblast) and H460 (human lung carcinoma) cell lines. The metabolites were also evaluated for immunomodulatory activity, and all were found to be inactive. IntroductionBiotransformation has been widely used in organic chemistry for stereoslective synthesis.1-6 Biotransformation reactions can be achieved by a variety of agents, such as enzymes, animals and plant cell cultures, and microorganisms; however, microorganisms are most effectively used for this purpose. Microbial enzyme systems can be used for reduction, oxidation, hydroxylation, and Michael addition. Regio-and stereo-selective oxidation and hydroxylation of steroids have been extensively achieved through microbial transformation. The cytochrome P450 monooxygenase system, present in microorganismsparticularly in fungi -is responsible for the stereoselective hydroxylation at various sites of the steroidal skeleton. 7-9Mestanolone (1) (C 20 H 18 O 2 ) is a member of the anabolicandrogenic class of steroids. It is weakly anabolic and strongly androgenic. Mestanolone was rst synthesized by the oxidation of 17b-methylandrostan-3b,17b-diol. It is used as a starting material for the synthesis of other anabolic steroids, such as 17-methyl-1-testosterone, and oxandrolone.10,11 Compound 1 was earlier subjected to microbial transformation, and several new analogues were obtained. 12In continuation of our research on biotransformation of bioactive compounds, and drug molecules, 13-15 mestanolone (1) was incubated with Macrophomina phaseolina, and Cunninghamella blakesleeana, which yielded metabolites 2-8 ( Fig. 1 and 2). ExperimentalGeneral Mestanolone (1) was acquired from Hangzhu Dayangchem (Cat no. 541-11-9, China). Sabouraud dextrose agar (SDA) was purchased from Merck KGaA (Cat no. 146392, Germany). Silica gel precoated TLC plates (PF 254 , Merck KGaA, Germany) were used for thin layer chromatography; phosphomolybdic acid solution was used as a staining reagent for UV inactive compounds. Silica gel (70-230 mesh, Merck, Germany) was used for column chromatography. Final purication of the compounds was carried out...

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Biotransformation of indomethacin by the fungus Cunninghamella blakesleeana1

Cited by 19 publications

References 9 publications

Biodegradation and biotransformation of polycyclic non-steroidal anti-inflammatory drugs

Biodegradation and biotransformation of polycyclic non-steroidal anti-inflammatory drugs

Biotransformation of metoprolol by the fungus Cunninghamella blakesleeana

Microbial transformation of mestanolone byMacrophomina phaseolinaandCunninghamella blakesleeanaand anticancer activities of the transformed products

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