51548-31-3Relevant academic research and scientific papers
Biotransformation of corticosteroids by Penicillium decumbens ATCC 10436
Holland, Herbert L.
, p. 646 - 649 (1995)
The biotransformation of a series of corticosteroids by the fungus Penicillium decumbens ATCC 10436 has been investigated. Conversion to the corresponding 5α-dihydroxteroid was observed for all the Δ4-3-ketosteroids studied with the exception of deoxycorticosterone, which was converted to a Δ14-diene. Deoxycorticosterone acetate was, however, converted to a 5α- dihydro product concomitant with ester hydrolysis. Other substrates carrying a C-21 acetoxy group were also hydrolyzed to the alcohol. In two cases (resulting from deoxycorticosterone acetate and 11-deoxycortisone) the 5α- 3-keto-product was further reduced to the 3β-alcohol. No reduction of δ14-dienes was observed.
INHIBITORS OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE FOR TREATING CARDIOVASCULAR AND PULMONARY CONDITIONS
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Page/Page column 41-42, (2018/06/06)
The present disclosure provides for methods of treating or preventing a cardiovascular disorder and/or a related pulmonary disorder in a subject. In certain embodiments, the method comprises administering a therapeutically effective amount of an inhibitor of Glucose-6-phosphate dehydrogenase (G6PD), or a pharmaceutically acceptable salt, non-salt amorphous form, solvate, poly-morph, tautomer or prodrug thereof.
Characterization of rabbit aldose reductase-like protein with 3β-hydroxysteroid dehydrogenase activity
Endo, Satoshi,Matsunaga, Toshiyuki,Kumada, Sho,Fujimoto, Airi,Hara, Akira,Ohno, Satoshi,El-Kabbani, Ossama,Hu, Dawei,Toyooka, Naoki,Mano, Jun'Ichi,Tajima, Kazuo
, p. 23 - 30,8 (2020/08/20)
In this study, we isolated the cDNA for a rabbit aldose reductase-like protein that shared an 86% sequence identity to human aldo-keto reductase (AKR)1 1B10 and has been assigned as AKR1B19 in the AKR superfamily. The purified recombinant AKR1B19 was similar to AKR1B10 and rabbit aldose reductase (AKR1B2) in the substrate specificity for various aldehydes and α-dicarbonyl compounds. In contrast to AKR1B10 and AKR1B2, AKR1B19 efficiently reduced 3-keto-5α/β-dihydro-C19/C21/C24-steroids into the corresponding 3β-hydroxysteroids, showing Km of 1.3-9.1 μM and kcat of 1.1-7.6 min-1. The stereospecific reduction was also observed in the metabolism of 5α- and 5β- dihydrotestosterones in AKR1B19-overexpressing cells. The mRNA for AKR1B19 was ubiquitously expressed in rabbit tissues, and the enzyme was co-purified with 3β-hydroxysteroid dehydrogenase activity from the lung. Thus, AKR1B19 may function as a 3-ketoreductase, as well as a defense system against cytotoxic carbonyl compounds in rabbit tissues. The molecular determinants for the unique 3-ketoreductase activity were investigated by replacement of Phe303 and Met304 in AKR1B19 with Gln and Ser, respectively, in AKR1B10. Single and double mutations (F303Q, M304S and F303Q/M304S) significantly impaired this activity, suggesting the two residues play critical roles in recognition of the steroidal substrate.
Novel steroid inhibitors of glucose 6-phosphate dehydrogenase
Hamilton, Niall M.,Dawson, Martin,Fairweather, Emma E.,Hamilton, Nicola S.,Hitchin, James R.,James, Dominic I.,Jones, Stuart D.,Jordan, Allan M.,Lyons, Amanda J.,Small, Helen F.,Thomson, Graeme J.,Waddell, Ian D.,Ogilvie, Donald J.
, p. 4431 - 4445 (2012/09/11)
Novel derivatives of the steroid DHEA 1, a known uncompetitive inhibitor of G6PD, were designed, synthesized, and tested for their ability to inhibit this dehydrogenase enzyme. Several compounds with approximately 10-fold improved potency in an enzyme assay were identified, and this improved activity translated to efficacy in a cellular assay. The SAR for steroid inhibition of G6PD has been substantially developed; the 3β-alcohol can be replaced with 3β-H-bond donors such as sulfamide, sulfonamide, urea, and carbamate. Improved potency was achieved by replacing the androstane nucleus with a pregnane nucleus, provided a ketone at C-20 is present. For pregnan-20-ones incorporation of a 21-hydroxyl group is often beneficial. The novel compounds generally have good physicochemical properties and satisfactory in vitro DMPK parameters. These derivatives may be useful for examining the role of G6PD inhibition in cells and will assist the future design of more potent steroid inhibitors with potential therapeutic utility.
