- Method of producing tibolone metabolites by fermentation with Rhizopus stolonifer
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A new method of producing metabolites of tibolone comprising fermenting tibolone with Rhizopus stolonifer (ATCC 12938) resulting in the formation of Δ4-Tibolone (C21H28O2), 6β-Hydroxytibolone, and 15β-Hydroxytibolone (C21H28O3) is reported.
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Page/Page column 12
(2012/04/10)
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- Liquid chromatography-mass spectrometry (LC-MS) of steroid hormone metabolites and its applications
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Advances in liquid chromatography-mass spectrometry (LC-MS) can be used to measure steroid hormone metabolites in vitro and in vivo. We find that LC-electrospray ionization (ESI)-MS using a LCQ ion trap mass spectrometer in the negative ion mode can be used to monitor the product profile that results from 5α-dihydrotestosterone (DHT)-17β-glucuronide, DHT-17β-sulfate, and tibolone-17β-sulfate reduction catalyzed by human members of the aldo-keto reductase (AKR) 1C subfamily and assign kinetic constants to these reactions. We also developed a stable isotope dilution LC-electron capture atmospheric pressure chemical ionization (ECAPCI)-MS method for the quantitative analysis of estrone (E1) and its metabolites as pentafluorobenzyl (PFB) derivatives in human plasma in the attomole range. The limit of detection for E1-PFB was 740. attomole on column. Separations can be performed using normal-phase LC because ionization takes place in the gas phase rather than in solution. This permits efficient separation of the regioisomeric 2- and 4-methoxy-E1. The method was validated for the simultaneous analysis of plasma E2 and its metabolites: 2-methoxy-E2, 4-methoxy-E2, 16α-hydroxy-E2, estrone (E1), 2-methoxy-E1, 4-methoxy-EI, and 16α-hydroxy-E1 from 5. pg/mL to 2000. pg/mL. Our LC-MS methods have sufficient sensitivity to detect steroid hormone levels in prostate and breast tumors and should aid their molecular diagnosis and treatment.
- Penning, Trevor M.,Lee, Seon-Hwa,Jin, Yi,Gutierrez, Alejandro,Blair, Ian A.
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experimental part
p. 546 - 555
(2011/12/02)
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- Alpha-glucosidase and tyrosinase inhibitors from fungal hydroxylation of tibolone and hydroxytibolones
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Sixteen new and one known metabolites 4-20 were obtained by incubation of tibolone (1) and hydroxytibolones (2 and 3) with various fungi. Their structures were elucidated by means of a homo and heteronuclear 2D NMR and by HREI-MS techniques. The relative stereochemistry was deduced by 2D NOESY experiment. Metabolites of tibolone (1) exhibited significant inhibitory activities against α-glucosidase and tyrosinase enzymes. Hydroxylations at C-6, C-10, C-11, C-15 positions and α,β-unsaturation at C-1/C-2, C-4/C-5 showed potent inhibitory activities against these enzymes.
- Choudhary, M. Iqbal,Shah, S. Adnan Ali,Atta-Ur-Rahman,Khan, Shamsun-Nahar,Khan, Mahmud Tareq Hassan
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experimental part
p. 956 - 966
(2010/10/05)
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- Enantioselective production of 3-hydroxy metabolites of tibolone by yeast reduction
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The enantioselective reduction of tibolone into the corresponding 3α-hydroxy or 3β-hydroxy metabolite can be controlled by choosing suited strains of yeasts and biotransformation conditions. A restricted screening performed among 52 yeasts showed that the 3α-epimer was preferentially obtained with high epimeric purity with various strains (i.e. with Kluyveromyces lactis CBS 2359), while only Saccharomyces cerevisiae CBS 3093 gave the 3β-epimer as major product. The reduction of tibolone with K. lactis CBS 2359 and S. cerevisiae CBS 3093 was optimised. S. cerevisiae CBS 3093 furnished a 96:4 ratio of 3β/3α with complete molar conversion within 72 h when the initial concentration of substrate was below 2.5 g/L. K. lactis CBS 2359 gave a 99:1 ratio of 3α/3β with complete conversion in 64 h.
- Romano, Diego,Ferrario, Valerio,Mora, Diego,Lenna, Roberto,Molinari, Francesco
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p. 112 - 115
(2008/03/30)
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- A practical chemoenzymatic approach to the synthesis of 3-hydroxy metabolites of tibolone
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Stereoselective preparation of the 3-hydroxy metabolites of tibolone is easily accomplished by diastereoselective Candida antarctica lipase B-catalyzed transformations of 3α- and 3β-alcohols or acetates mixtures in organic solvents, in suitable amounts for biological studies.
- Ferraboschi, Patrizia,Colombo, Diego,Reza-Elahi, Shahrzad
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p. 2583 - 2586
(2007/10/03)
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- Stereochemical analysis of the 3α- and 3β-hydroxy metabolites of tibolone through NMR and quantum-chemical investigations. An experimental test of GIAO calculations
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The configuration at C-3 of the 3α- and 3β-hydroxy metabolites of tibolone was studied by extensive application of one- and two-dimensional 1H and 13C NMR spectroscopy combined with molecular modeling performed at the B3LYP/6-31G(d)
- Colombo, Diego,Ferraboschi, Patrizia,Ronchetti, Fiamma,Toma, Lucio
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p. 581 - 588
(2007/10/03)
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