1164-98-3Relevant articles and documents
An improved synthesis of the corticoid side chain
Daniewski,Wojciechowska
, p. 132 - 134 (1984)
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Synthesis of the corticoid side chain
Daniewski,Wojciechowska
, p. 2993 - 2995 (1982)
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Resolving entangled jh-h-coupling patterns for steroidal structure determinations by nmr spectroscopy
Wu, Danni,Carillo, Kathleen Joyce,Shie, Jiun-Jie,Yu, Steve S.-F.,Tzou, Der-Lii M.
, (2021)
For decades, high-resolution1H NMR spectroscopy has been routinely utilized to analyze both naturally occurring steroid hormones and synthetic steroids, which play important roles in regulating physiological functions in humans. Because the1H signals are inevitably superimposed and entangled with various JH–H splitting patterns, such that the individual1H chemical shift and associated JH–H coupling identities are hardly resolved. Given this, applications of thess information for elucidating steroidal molecular structures and steroid/ligand interactions at the atomic level were largely restricted. To overcome, we devoted to unraveling the entangled JH–H splitting patterns of two similar steroidal compounds having fully unsaturated protons, i.e., androstanolone and epiandrosterone (denoted as 1 and 2, respectively), in which only hydroxyl and ketone substituents attached to C3 and C17 were interchanged. Here we demonstrated that the JH–H values deduced from 1 and 2 are universal and applicable to other steroids, such as testosterone, 3β, 21-dihydroxygregna5-en-20-one, prednisolone, and estradiol. On the other hand, the1H chemical shifts may deviate substantially from sample to sample. In this communication, we propose a simple but novel scheme for resolving the complicate JH–H splitting patterns and1H chemical shifts, aiming for steroidal structure determinations.
Effects of fluorine substitution on substrate conversion by cytochromes P450 17A1 and 21A2
Vogt, Caleb D.,Bart, Aaron G.,Yadav, Rahul,Scott, Emily E.,Aubé, Jeffrey
, p. 7664 - 7669 (2021/09/22)
Cytochromes P450 17A1 (CYP7A1) and 21A2 (CYP21A2) catalyze key reactions in the production of steroid hormones, including mineralocorticoids, glucocorticoids, and androgens. With the ultimate goal of designing probes that are selectively metabolized to each of these steroid types, fluorinated derivatives of the endogenous substrates, pregnenolone and progesterone, were prepared to study the effects on CYP17A1 and CYP21A2 activity. In the functional assays, the hydroxylase reactions catalysed by each of these enzymes were blocked when fluorine was introduced at the site of metabolism (positions 17 and 21 of the steroid core, respectively). CYP17A1, furthermore, performed the 17,20-lyase reaction on substrates with a fluorine installed at the 21-position. Importantly, none of the substitutions examined herein prevented compound entry into the active sites of either CYP17A1 or CYP21A2 as demonstrated by spectral binding assays. Taken together, the results suggest that fluorine might be used to redirect the metabolic pathways of pregnenolone and progesterone to specific types of steroids.
A new steroidal 5,7-diene derivative, 3β-hydroxyandrosta-5,7-diene-17β-carboxylic acid, shows potent anti-proliferative activity
Kim, Tae-Kang,Chen, Jianjun,Li, Wei,Zjawiony, Jordan,Miller, Duane,Janjetovic, Zorica,Tuckey, Robert C.,Slominski, Andrzej
experimental part, p. 230 - 239 (2010/04/29)
The new steroidal 5,7-diene, 3β-hydroxyandrosta-5,7-diene-17β-carboxylic acid (17-COOH-7DA), was synthesized from 21-acetoxypregnenolone, with the oxidative cleavage of the side chain being dependent on the presence of oxygen. In human epidermal (HaCaT) keratinocytes, 17-COOH-7DA inhibited proliferation in a dose-dependent manner, starting at a dose as low as 10-11 M. This inhibition was accompanied by decreased expression of epidermal growth factor receptor, bcl2 and cyclin E2 mRNAs and by increased expression of involucrin mRNA. Inhibition of proliferation was associated with slowing of the cell cycle in G1/G0 phases but not with cell death. 17-COOH-7DA was significantly more potent than pregnenolone, 17-COOH-pregnenolone, 17-COOCH3-7DA and calcitriol. 17-COOH-7DA also inhibited proliferation of normal human epidermal melanocytes and human and hamster melanoma lines, however, with lower potency than for keratinocytes. In normal human dermal fibroblasts 17-COOH-7DA stimulated proliferation in serum-free media but inhibited it in the presence of 5% serum. 17-COOH-7DA inhibited cell colony formation of human and hamster melanoma cells, and induced monocyte-like differentiation of human HL60 leukemia cells. Thus, the new steroidal 5,7-diene, 17-COOH-7DA, can serve as an inhibitor of proliferation of normal keratinocytes and normal and malignant melanocytes, as a condition-dependent regulator of fibroblast proliferation and a stimulator of leukemia cell differentiation.
