- Biotransformation of hydrocortisone by a natural isolate of Nostoc muscorum
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Hydrocortisone was converted in the culture of an isolated strain of the cyanobacterium Nostoc muscorum PTCC 1636 into some androstane and pregnane derivatives. The microorganism was isolated during a screening program from soil samples collected from paddy fields of north of Iran. The bioproducts obtained were purified using chromatographic methods and identified as 11β-hydroxytestosterone, 11β-hydroxyandrost-4-en-3,17-dione and 11β,17α,20β,21-tetrahydroxypregn-4-en-3-one on the basis of their spectroscopic features.
- Yazdi, Mojtaba Tabatabaei,Arabi, Homeira,Faramarzi, Mohammad Ali,Ghasemi, Younes,Amini, Mohsen,Shokravi, Shadman,Mohseni, Farzaneh Aziz
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- Raw synthesis and mitochondrial function postischemic mitochondria diseases related to the lack or for use in new compd. 11β-hydroxysteroid
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The present invention provides novel compounds of 112-hydroxy steroids and compositions and their application as pharmaceuticals for preventing or reversing injury to mitochondria, for treating or preventing diseases relating to mitochondrial dysfunction or depletion, and for inducing regeneration or restructuring of mitochondria as a means of treating diseases relating to abnormalities in mitochondrial structure and function in a human or animal subject. Also disclosed herein are methods for diagnosing injury to mitochondria and for diagnosing the success or failure of therapeutics designed to treat, prevent, or reverse injury to or depletion of mitochondria.
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Paragraph 0248; 0275
(2016/10/08)
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- Microbial Baeyer-Villiger oxidation of 5α-steroids using Beauveria bassiana. A stereochemical requirement for the 11α-hydroxylation and the lactonization pathway
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Beauveria bassiana KCH 1065, as was recently demonstrated, is unusual amongst fungal biocatalysts in that it converts C19 3-oxo-4-ene and 3β-hydroxy-5-ene as well as 3β-hydroxy-5α-saturated steroids to 11α-hydroxy ring-D lactones. The Baeyer-Villiger monooxygenase (BVMO) of this strain is distinguished from other enzymes catalyzing BVO of steroidal ketones by the fact that it oxidizes solely substrates with 11α-hydroxyl group. The current study using a series of 5α-saturated steroids (androsterone, 3α-androstanediol and androstanedione) has highlighted that a small change of the steroid structure can result in significant differences of the metabolic fate. It was found that the 3α-stereochemistry of hydroxyl group restricted "normal" binding orientation of the substrate within 11α-hydroxylase and, as a result, androsterone and 3α-androstanediol were converted into a mixture of 7β-, 11α- and 7α-hydroxy derivatives. Hydroxylation of androstanedione occurred only at the 11α-position, indicating that the 3-oxo group limits the alternative binding orientation of the substrate within the hydroxylase. Only androstanedione and 3α-androstanediol were metabolized to hydroxylactones. The study uniquely demonstrated preference for oxidation of equatorial (11α-, 7β-) hydroxyketones by BVMO from B. bassiana. The time course experiments suggested that the activity of 17β-HSD is a factor determining the amount of produced ring-D lactones. The obtained 11α-hydroxylactones underwent further transformations (oxy-red reactions) at C-3. During conversion of androstanedione, a minor dehydrogenation pathway was observed with generation of 11α,17β-dihydroxy-5α-androst-1-en-3-one. The introduction of C1C2 double bond has been recorded in B. bassiana for the first time.
- ?wizdor, Alina,Panek, Anna,Milecka-Tronina, Natalia
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- C-20 ketone reduction of hydrocortisone by rice field microalga Chlorella vulgaris MCCS 013
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A unicellular microalga, Chlorella vulgaris, was isolated from rice field and applied in the biotransformation experiment of hydrocortisone (1). This strain has not been previously tested for hydrocortisone bioconversion. Fermentation was carried out in B
- Ghasemi, Younes,Rasoul-Amini, Sara,Morowvat, Mohammad Hossein,Ghoshoon, Mohammad Bagher,Raee, Mohammad Javad,Khoubani, Soraya,Negintaji, Narges,Nouri, Fatemeh,Parvizi, Rezvan
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experimental part
p. 824 - 828
(2010/08/19)
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- Synthesis of 11β-Fluoro-5α-dihydrotestosterone and 11β-Fluoro-19-nor-5α-dihydrotestosterone: Preparation via Halofluorination-Reduction, Receptor Binding, and Tissue Distribution
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We have prepared 11β-fluoro-5α-dihydrotestosterone (11β-F-DHT, 1) and 11β-fluoro-19-nor-5α-dihydrotestosterone (11β-F-19-nor-DHT, 2) in order to investigate the properties of these new androgens labeled with fluorine-18 as potential androgen receptor (AR)-based imaging agents for prostate cancer.These compounds were synthesized in 6 steps from hydrocortisone and in 13 steps from 1,4-androstadiene-3,11,17-trione, respectively.Relative binding affinities (RBA) of 11β-F-DHT and 11β-F-19-nor-DHT to AR are 53.1 and 75.3 (R1881 = 100), respectively, the latter being the highest reported among fluorine-substituted androgens.The fluorination step, which involves addition of halogen fluoride across the 9(11)-double bond, followed by reductive dehalogenation at the 9α-position has been adapted to introduce a fluorine-18-label at the 11β-position of DHT and 19-nor-DHT.The two high-affinity F-18-labeled ligands -1 and -2 were evaluated in vivo, in tissue distribution studies using diethylstilbestrol-pretreated mature male rats. 11β-F-DHT shows high prostate uptake and selective prostate to blood and prostate to muscle uptake ratios, the latter two ratios increasing from 5 and 8 at 1 h to 12 and 19 at 4 h postinjection.Moreover, this compound has low uptake in bone, displaying the lowest in vivo defluorination among all androgens labeled with fluorine-18 tested so far.The in vivo properties of 11β-F-DHT in rats are thus favorable for imaging of prostate cancer.On the other hand, 11β-F-19-nor-DHT shows low prostate uptake with low selectivity and high uptake in liver, kidney, and bladder.Even though this ligand has the highest RBA and undergoes little metabolic defluorination, it appears to suffer from rapid metabolism in vivo.Therefore, it is apparent that the biodistribution properties of androgens are affected by their structure and metabolism as well as by their RBA.
- Choe, Yearn Seong,Lidstroem, Pelle J.,Chi, Dae Yoon,Bonasera, Thomas A.,Welch, Michael J.,Katzenellenbogen, John A.
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p. 816 - 825
(2007/10/02)
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- Synthesis of 11-substituted androstenediones and testosterones as human decidual cell growth inhibitors
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11α-Hydroxytestosterone (1a), 11β-hydroxytestosterone (1b), 11α- methoxytestosterone (1c), 11β-methoxytestosterone (1d), 11-ketotestosterone (1e), and Δ(9(11))-testosterone (1f) were synthesized from hydrocortisone (4b) or 11-epi-hydrocortisone (4a). The six target compounds, together with 11α-methoxyandrostenedione (2c), 11β-methoxyandrostenedione, (2d) and their lead compound, testosterone (1), were found to effectively inhibit the growth and differentiation of human decidual cells in culture. There is no observable binding of these compounds to estrogen receptor of rabbit uterus. The introduction of a polar group (e.g., hydroxyl and carbonyl) to C-11 of androstenes decreases both the relative binding affinities to progesterone receptor and the inhibitory effects on human decidual cell growth, while the methylation of 11-hydroxyl group minimizes these effects. The similar effects of a polar group at C-11 of testosterone (1) on the inhibitory effects on human decidual cell growth and the relative binding affinities to progesterone receptor of rabbit uterus may suggest that one of the mechanisms of human decidual cell growth inhibition by these compounds is the anti- progestational activity of these androgens.
- Zhao, Qinjian,Li, Zhensu
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p. 190 - 195
(2007/10/02)
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