- The generation of a steroid library using filamentous fungi immobilized in calcium alginate Dedicated to the memory of Professor Sir John W. Cornforth, University of Sussex (1917-2013).
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Four fungi, namely, Rhizopus oryzae ATCC 11145, Mucor plumbeus ATCC 4740, Cunninghamella echinulata var. elegans ATCC 8688a, and Whetzelinia sclerotiorum ATCC 18687, were subjected to entrapment in calcium alginate, and the beads derived were used in the biotransformation of the steroids 3β,17β-dihydroxyandrost-5-ene (1) and 17β-hydroxyandrost-4-en-3-one (2). Incubations performed utilized beads from two different encapsulated fungi to explore their potential for the production of metabolites other than those derived from the individual fungi. The investigation showed that steroids from both single and crossover transformations were typically produced, some of which were hitherto unreported. The results indicated that this general technique can be exploited for the production of small libraries of compounds.
- Peart, Patrice C.,Reynolds, William F.,Reese, Paul B.
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- Hydroxylation of DHEA and its analogues by Absidia coerulea AM93. Can an inducible microbial hydroxylase catalyze 7α- and 7β-hydroxylation of 5-ene and 5α-dihydro C19-steroids?
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In this paper we focus on the course of 7-hydroxylation of DHEA, androstenediol, epiandrosterone, and 5α-androstan-3,17-dione by Absidia coerulea AM93. Apart from that, we present a tentative analysis of the hydroxylation of steroids in A. coerulea AM93. DHEA and androstenediol were transformed to the mixture of allyl 7-hydroxy derivatives, while EpiA and 5α-androstan-3,17-dione were converted mainly to 7α- and 7β-alcohols accompanied by 9α- and 11α-hydroxy derivatives. On the basis of (i) time course analysis of hydroxylation of the abovementioned substrates, (ii) biotransformation with resting cells at different pH, (iii) enzyme inhibition analysis together with (iv) geometrical relationship between the C-H bond of the substrate undergoing hydroxylation and the cofactor-bound activated oxygen atom, it is postulated that the same enzyme can catalyze the oxidation of C7-Hα as well as C7-H β bonds in 5-ene and 5α-dihydro C19-steroids. Correlations observed between the structure of the substrate and the regioselectivity of hydroxylation suggest that 7β-hydroxylation may occur in the normal binding enzyme-substrate complex, while 7α-hydroxylation - in the reverse inverted binding complex.
- Milecka-Tronina, Natalia,Ko?ek, Teresa,?wizdor, Alina,Panek, Anna
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p. 883 - 891
(2014/01/23)
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- Biotransformation of 3β-hydroxy-5-en-steroids by Mucor silvaticus
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The biotransformation of four 3β-hydroxy-5-en-steroids with varying substituents at C-16 or/and C-17 by Mucor silvaticus was investigated. The characterization of the metabolites was performed by IR, MS, 1H NMR, 13C NMR, and 2-D NMR.
- Wang, Yanjie,Sun, Dongmei,Chen, Zhibao,Ruan, Hongsheng,Ge, Wenzhong
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p. 168 - 174
(2013/09/12)
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- Hydroxylation of DHEA, androstenediol and epiandrosterone by Mortierella isabellina AM212. Evidence indicating that both constitutive and inducible hydroxylases catalyze 7α- as well as 7β-hydroxylations of 5-ene substrates
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The course of transformation of DHEA, androstenediol and epiandrosterone in Mortierella isabellina AM212 culture was investigated. The mentioned substrates underwent effective hydroxylation; 5-ene substrates - DHEA and androstenediol - were transformed into a mixture of 7α- and 7β- allyl alcohols, while epiandrosterone was converted into 7α- (mainly), 11α- and 9α- monohydroxy derivatives. Ketoconazole and cycloheximide inhibition studies suggest the presence of constitutive and substrate-induced hydroxylases in M. isabellina. On the basis of time course analysis of the hydroxylation of DHEA and androstenediol, the oxidation of allyl C7-Hα and C7-Hβ bonds by the same enzyme is a reasonable assumption.
- Kolek, Teresa,Milecka, Natalia,Swizdor, Alina,Panek, Anna,Bialonska, Agata
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scheme or table
p. 5414 - 5422
(2011/09/13)
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- C19-Steroids as androgen receptor modulators: Design, discovery, and structure-activity relationship of new steroidal androgen receptor antagonists
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Dehydroepiandrosterone (DHEA), the most abundant steroid in human circulating blood, is metabolized to sex hormones and other C19-steroids. Our previous collaborative study demonstrated that androst-5-ene-3β,17β-diol (Adiol) and androst-4-ene-3,17-dione (Adione), metabolites of DHEA, can activate androgen receptor (AR) target genes. Adiol is maintained at a high concentration in prostate cancer tissue; even after androgen deprivation therapy and its androgen activity is not inhibited by the antiandrogens currently used to treat prostate cancer patients. We have synthesized possible metabolites of DHEA and several synthetic analogues and evaluated their role in androgen receptor transactivation to identify AR modulators. Steroids with low androgenic potential in PC-3 cell lines were evaluated for anti-dihydrotestosterone (DHT) and anti-Adiol activity. We discovered three potent antiandrogens: 3β-acetoxyandrosta-1,5-diene-17-one 17-ethylene ketal (ADEK), androsta-1,4-diene-3,17-dione 17-ethylene ketal (OAK), and 3β-hydroxyandrosta-5,16-diene (HAD) that antagonized the effects of DHT as well as of Adiol on the growth of LNCaP cells and on the expression of prostate-specific antigen (PSA). In vivo tests of these compounds will reveal their potential as potent antiandrogens for the treatment of prostate cancer.
- Marwah, Padma,Marwah, Ashok,Lardy, Henry A.,Miyamoto, Hiroshi,Chang, Chawnshang
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p. 5933 - 5947
(2007/10/03)
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- Steroid transformations with Fusarium oxysporum var. cubense and Colletotrichum musae
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The utility of two locally isolated fungi, pathogenic to banana, for steroid biotransformation has been studied. The deuteromycetes Fusarium oxysporum var. cubense (IMI 326069, UAMH 9013) and Colletotrichum musae (IMI 374528, UAMH 8929) had not been examined previously for this potential. In general, F. oxysporum var. cubense effected 7α hydroxylation on 3β-hydroxy- Δ5-steroids, 6β, 12β, and 15α hydroxylation on steroidal-4-ene-3-ones, side-chain degradation on 17α,21-dihydroxypregnene-3,20-diones, and 15α hydroxylation on estrone. Both strains were shown to perform redox reactions on alcohols and ketones.
- Wilson, Maureen R.,Gallimore, Winklet A.,Reese, Paul B.
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p. 834 - 843
(2007/10/03)
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- Regulation of the immune system
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The addition of 5-androstene 3β,17βdiol and/or 5-androstene 3β,7β,17β triol to growth media increases proliferation of lymphocytes in culture. By methods of the invention it is possible to increase production of autogenous lymphocytes for administration to the patient.
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- Enhancement of immune response
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The present invention provides an improved means for regulating the immune response, for ameliorating effects of stress, and for avoiding untoward effects of chemotherapy or exposure to irradiation by administration of androstenediol (AED) and androstenetriol (AET). The improved means of regulating immune response can be utilized in treating infectious diseases and immune diseases such as diabetes and chronic fatigue syndrome, both diseases now considered to be immune response related syndromes.
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