145-15-3Relevant articles and documents
PROGESTERONE-CATIONIC LIPID HYBRID AS ANTICANCER AGENT AND THE PROCESS OF SYNTHESIS THEREOF
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Paragraph 0033; 0034; 0046; 0047; 0048; 0049, (2018/02/28)
The present invention relates to the development of the cationic progesterone compounds of formula 6 as a novel anti-tumor agent. The present invention provides a method for the preparation of novel series of progesterone derivatives of formula 6. The invention also provides information related to highly selective anti-cancer activities of these compounds in wide range of cancer cell irrespective of their progesterone receptor status. Thus, the presently disclosed cationic progesterone compounds offer a viable option as anti-cancer therapeutics.
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.
Rabbit 3-hydroxyhexobarbital dehydrogenase is a NADPH-preferring reductase with broad substrate specificity for ketosteroids, prostaglandin D2, and other endogenous and xenobiotic carbonyl compounds
Endo, Satoshi,Matsunaga, Toshiyuki,Matsumoto, Atsuko,Arai, Yuki,Ohno, Satoshi,El-Kabbani, Ossama,Tajima, Kazuo,Bunai, Yasuo,Yamano, Shigeru,Hara, Akira,Kitade, Yukio
, p. 1366 - 1375 (2013/11/19)
3-Hydroxyhexobarbital dehydrogenase (3HBD) catalyzes NAD(P) +-linked oxidation of 3-hydroxyhexobarbital into 3-oxohexobarbital. The enzyme has been thought to act as a dehydrogenase for xenobiotic alcohols and some hydroxysteroids, but its physiological function remains unknown. We have purified rabbit 3HBD, isolated its cDNA, and examined its specificity for coenzymes and substrates, reaction directionality and tissue distribution. 3HBD is a member (AKR1C29) of the aldo-keto reductase (AKR) superfamily, and exhibited high preference for NADP(H) over NAD(H) at a physiological pH of 7.4. In the NADPH-linked reduction, 3HBD showed broad substrate specificity for a variety of quinones, ketones and aldehydes, including 3-, 17- and 20-ketosteroids and prostaglandin D2, which were converted to 3α-, 17β- and 20α-hydroxysteroids and 9α,11β- prostaglandin F2, respectively. Especially, α-diketones (such as isatin and diacetyl) and lipid peroxidation-derived aldehydes (such as 4-oxo- and 4-hydroxy-2-nonenals) were excellent substrates showing low Km values (0.1-5.9 μM). In 3HBD-overexpressed cells, 3-oxohexobarbital and 5β-androstan-3α-ol-17-one were metabolized into 3-hydroxyhexobarbital and 5β-androstane-3α,17β-diol, respectively, but the reverse reactions did not proceed. The overexpression of the enzyme in the cells decreased the cytotoxicity of 4-oxo-2-nonenal. The mRNA for 3HBD was ubiquitously expressed in rabbit tissues. The results suggest that 3HBD is an NADPH-preferring reductase, and plays roles in the metabolisms of steroids, prostaglandin D2, carbohydrates and xenobiotics, as well as a defense system, protecting against reactive carbonyl compounds.
Development and screening of water-soluble analogues of progesterone and allopregnanolone in models of brain injury
MacNevin, Christopher J.,Atif, Fahim,Sayeed, Iqbal,Stein, Donald G.,Liotta, Dennis C.
experimental part, p. 6012 - 6023 (2010/02/28)
Preclinical and clinical research findings have revealed that the hormone progesterone, when acutely administered, can dramatically reduce cerebral edema, inflammation, tissue necrosis, and programmed cell death following traumatic brain injury (TBI). The poor aqueous solubility of progesterone, however, limits its potential use as a therapeutic. Several chemically novel analogues of progesterone and its natural metabolite allopregnanolone have been synthesized and screened using both in vitro and whole animal models of TBI. The new derivatives demonstrated greatly improved solubility and select compounds have shown equivalent effectiveness to progesterone in reducing cerebral edema after TBI. 2009 American Chemical Society.
An efficient enzymatic preparation of 20-pregnane succinates: chemoenzymatic synthesis of 20β-hemisuccinyloxy-5αH-pregnan-3-one
Monsalve, Leandro N.,Machado Rada, Mayra Y.,Ghini, Alberto A.,Baldessari, Alicia
, p. 1721 - 1730 (2008/09/19)
Lipase-catalyzed transesterification of the 20 hydroxyl group in a series of pregnanes afforded novel 20-ethyl succinates that are not possible to prepare following the traditional synthetic methods. The reaction is stereoselective. The enzyme reacts selectively with the 20β epimers therefore only the 20β-succinyloxy derivatives are obtained. These compounds are obtained in variable yield, depending on the substitution in the ring A. The enzymatic approach allowed, for the first time, the synthesis of 20β-hemisuccinyloxy-5αH-pregnan-3-one, novel compound useful as a precursor of steroid-protein conjugates.
PROCESS FOR PREPARING GUGGULSTERONES AND GUGGULSTEROL
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Page 23; 51-52, (2010/02/09)
The present invention relates to a method for selective preparing 4,17 (20)-E-pregnadiene-3,16-dione (E-guggulsterone) of the formula (III) and 4,17 (20)-Z-pregnadiene-3,16-dione (Z-guggulsterone) of the formula (IV) having an effect of lowering the elevated low density lipoprotein (LDL) and high levels of the cholesterol effectively, and elevating the low levels of the high density lipoprotein (HDL) from a easy-available steroid of the following formula (I). Also, the present invention provides a method for preparation of the compound of the above formula (II).
HYDROXYLATION OF PROGESTERONE BY CEPHALOSPORIUM APHIDICOLA
Farooq, Afgan,Hanson, James R.,Iqbal, Zahida
, p. 723 - 726 (2007/10/02)
The fungus, Cephalosporium aphidicola, has been shown to hydroxylate progesterone predominantly at the 6β- and 11α-positions.Minor metabolites include tetstosterone acetate, the 20(R)-alcohol and 12β,17α-dihydroxyprogesterone.The sequence involves hydroxylation at 11α and then 6β.The hydroxylations of 11α- and 17α-hydroxyprogesterone and 9β,10α-retroprogesterone have also been examined in the light of these results. - Key words: Cephalosporium aphidicola; progesterone; 9β,10α-retroprogesterone; steroid; microbiological hydroxylation.
Steroids and Related Studies: Part 79 - Pregnano-1',2',5'-oxadiazol-20-ones
Jindal, Dharam Paul,Yadav, Mange Ram,Sharma, Rakesh K.,Agrawal, Vijaykumar R.,Singh, Harkishan
, p. 100 - 103 (2007/10/02)
5β-Pregnano-1',2',5'-oxadiazol-20-one (1) and its 5α-epimer (2) have been obtained by catalytic reduction of the respective 16-pregneno-1',2',5'-oxadiazol-20-ones (3 and 4).Another approach towards 1 and 2 involves preparation of (20R)-4,20-dihydroxy-4-pregnen-3-one (9) or its 20-acetate (8), conversion to dioximes (10 and 11), heating the latter with alkali and oxidising the resulting 20-hydroxyoxadiazoles (12 and 13) to the respective 20-ones (1 and 2).
Modification of steroidogenesis in a mouse adrenal cell line (Y-1) transformed by simian adenovirus SA-7.
Lefevre,Faucon-Biguet,Mathieu,Tournier,Saez
, p. 315 - 325 (2007/10/02)
Transformation of a steroidogenic mouse adrenal cell line (Y-1) by simian adenovirus SA7 produced a cell line with low apparent steroidogenic activity. The effect of ACTH and cholera toxin on cyclic AMP production was similar in both not transformed and virus-transformed cells and activity of cyclic AMP-dependent protein kinase was also similar in both cells. In transformed cells, cholesterol was metabolized to delta 5-3 beta-hydroxysteroids, mainly 20 alpha-dihydropregnenolone while in not transformed cells, the major metabolites were delta 4-3 ketosteroids (20 alpha-dihydro- and 11 beta-hydroxy-20 alpha-dihydroprogesterone). In both cell lines ACTH increased the metabolism of cholesterol. Further studies with labelled pregnenolone and progesterone revealed a loss of delta 5-3 beta-hydroxysteroid dehydrogenase/isomerase and 11 beta-hydroxylase activity in the transformed cells.
Lithium Aluminium Hydride Reduction of Pregnenolone under Conditions of Assumed Kinetic and Equilibrium Control
Allenmark, Stig,Boren, Hans
, p. 407 - 410 (2007/10/02)
Reduction of pregnenolone (1) with lithium aluminium hydride (LAH) yields pregn-5-ene-3β,20α-diol (2a) and its 20β epimer (2b) in a ratio of 1:3.8.Reduction with LAH/AlCl3 under equilibrating conditions, using an excess of 1, gave a complex product mixture containing 2a and 2b in a ratio of 1:9, pregna-3,5-dien-20-one (3), pregna-3,5-dien-20-ols (4a and 4b), pregn-4-ene-20α-ol-3-one (6a), its 20β epimer (6b) as well as small amounts of other compounds, probably pregn-4-ene-3,20-diols.A reaction scheme is presented which accounts for the formation of the various reaction products.
