60966-95-2Relevant academic research and scientific papers
Substrate specificity and inhibitor sensitivity of rabbit 20α-hydroxysteroid dehydrogenase
Endo, Satoshi,Arai, Yuki,Hara, Akira,Kitade, Yukio,Bunai, Yasuo,El-Kabbani, Ossama,Matsunaga, Toshiyuki
, p. 1514 - 1518 (2013/10/08)
In this study, we examined the substrate specificity and inhibitor sensitivity of rabbit 20α-hydroxysteroid dehydrogenase (AKR1C5), which plays a role in the termination of pregnancy by progesterone inactivation. AKR1C5 moderately reduced the 3-keto group of only 5α-dihydrosteroids with 17β- or 20α/β-hydroxy group among 3-ketosteroids. In contrast, the enzyme reversibly and efficiently catalyzed the reduction of various 17- and 20-ketosteroids, including estrogen precursors (dehydroepiandrosterone, estrone and 5α-androstan-3β- ol-17-one) and tocolytic 5β-pregnane-3,20- dione. In addition to the progesterone inactivation, the formation of estrogens and metabolism of the tocolytic steroid by AKR1C5 may be related to its role in rabbit parturition. AKR1C5 also reduced various non-steroidal carbonyl compounds, including isatin, an antagonist of the C-type natriuretic peptide receptor, and 4-oxo-2-nonenal, suggesting its roles in controlling the bioactive isatin and detoxification of cytotoxic aldehydes. AKR1C5 was potently and competitively inhibited by flavonoids such as kaempferol and quercetin, suggesting that its activity is affected by ingested flavonoids.
Neurosteroid analogues. 4. The effect of methyl substitution at the C-5 and C-10 positions of neurosteroids on electrophysiological activity at GABA(A) receptors
Han, Mingcheng,Zorumski, Charles F.,Covey, Douglas F.
, p. 4218 - 4232 (2007/10/03)
A series of analogues of the neuroactive steroids 3α-hydroxy-5α- pregnan-20-one and 3α-hydroxy-5β-pregnan-20-one were studied to elucidate the mode of binding of 5α- and 5β-reduced steroids to steroid binding sites on GABA(A) receptors. Analogues which were either 3α-hydroxy-20-ketosteroids or 3α-hydroxysteroid-17β-carbonitriles and which contained various methyl group substitution patterns at C-5 and C-10 were prepared. Evaluations utilized whole-cell patch clamp electrophysiological methods carried out on cultured rat hippocampal neurons, and the results obtained with the rigid 17β-carbonitrile analogs were analyzed using molecular modeling methods. The molecular modeling results provide a rationale for the observation that the configuration of the hydroxyl group at C-3 is a greater determinant of anesthetic potency than the configuration of the A,B ring fusion at C-5. The electrophysiological results identify steric restrictions for the space that can be occupied in 5α- and 5β-reduced steriod modulators of GABA(A) recepters in the regions of space proximate to the steroid C-5, C-10, and possibly C-4 positions. This information is useful for the development of nonsteroidal analogues that can modulate GABA(A) receptors via interactions at steroid binding sites.
SYNTHESIS AND CHARACTERISTICS OF ALLYLIC 4-PREGNENE-3,20-DIOLS FOUND IN GONADAL AND BREAST TISSUES
Wiebe, J. P.,Dave, Vinod,Stothers, J. B.
, p. 249 - 260 (2007/10/02)
Recently several allylic steroids have been found in gonadal and breast tissues.In order to establish their presence and identity in tissues and determine the possible biological properties, a method for the synthesis of 4-pregnene-3α,20α-diol, 4-pregnene-3α,20β-diol, 4-pregnene-3β,20α-diol, and 4-pregnene-3β,20β-diol was developed using 4-pregnene-3,20-dione (progesterone) as substrate and freshly-prepared aluminum isopropoxide in isopropyl alcohol as reducing agent.The yields were about 19percent, 30percent, 13percent, and 38percent for the 3α,20α-, 3α,20β-, 3β,20α-, and 3β,20β-diols, respectively.The structures and stereochemistry of these diols were established using proton and carbon NMR spectroscopy and infrared and mass spectrometry.
Synthesis of the allylic gonadal steroids, 3α-hydroxy-4-pregnen-20-one and 3α-hydroxy-4-androsten-17-one, and of 3α-hydroxy-5α-pregnan-20-one
Wiebe,Deline,Buckingham
, p. 39 - 51 (2007/10/02)
A method for the convenient synthesis of the recently isolated allylic gonadal steroids, 3α-hydroxy-4-pregnen-20-one (3α-dihydroprogesterone; 3α-DHP) and 3α-hydroxy-4-androsten-17-one (3α-HA), was developed using 4-pregnene-3,20-dione (progesterone) and 4-androstene-3,17-dione as substrates and potassium trisiamylborohydride (KS-Selectride) as reducing agent. Similar reactions were also used for the reduction of 5α-pregnane-3,20-dione to 3α-hydroxy-5α-pregnan-20-one (3α-HP). The yields were about 15%, 50%, and >90% for 3α-DHP, 3α-HA and 3α-HP, respectively. Structures of the products, including the 3β-isomers and the 17α-epimer, formed in these reactions were determined by NMR and mass spectroscopic methods.
