1162-53-4Relevant articles and documents
Microwave-assisted stereoselective approach to novel steroidal ring D-fused 2-pyrazolines and an evaluation of their cell-growth inhibitory effects in vitro
Mótyán, Gergo,Kovács, Ferenc,W?lfling, János,Gyovai, András,Zupkó, István,Frank, éva
, p. 36 - 46 (2016)
Novel ring D-condensed 2-pyrazolines in the Δ5-androstene series were efficiently synthesized from 16-dehydropregnenolone or its acetate with different arylhydrazines or methylhydrazine, respectively, under microwave irradiation. The reactions are assumed to occur via hydrazone intermediates, followed by intramolecular 1,4-addition leading to the fused heteroring stereoselectively with a 16α,17α-cis ring junction. The synthesized compounds were subjected to in vitro pharmacological studies of their antiproliferative activities against four human breast (MCF7, T47D, MDA-MB-231 and MDA-MB-361) and three cervical (HeLa, C33A and SiHA) malignant cell lines. Flow cytometry revealed that the most potent agent elicited a cell cycle disturbance.
Synthesis and characterization of new phenyl esters derived from 16-dehydropregnenolone acetate (16-DPA)
Li, Hongqi,Fang, Jueshu,Li, Juan,Wang, Yulong,Tian, Xiujuan,Xiang, Yuanhui
, p. 3887 - 3893 (2013)
A series of new phenyl esters based on a 5,16-pregnadiene-20-one skeleton, namely 3β-benzoyloxy-5,16-pregnadiene-20-ones, which may be good inhibitors of 17α-hydroxylase and 5α-reductase enzyme or useful intermediates for producing steroidal drugs, were synthesized starting from diosgenin. The structures of the steroids were characterized by 1H nuclear magnetic resonance (NMR), 13C NMR, infrared (IR), and mass spectra.
Allimacrosides A–E, new steroidal glycosides from Allium macrostemon Bunge
Kim, Yun Sik,Suh, Won Se,Park, Kyoung Jin,Choi, Sang Un,Lee, Kang Ro
, p. 41 - 46 (2017)
A new pregnane-type steroidal glycoside (1), two new spirostane-type steroidal glycosides (2, 3), and two new furostane-type steroidal glycosides (4, 5), named allimacrosides A–E, together with four known compounds (6–9) were isolated from a 80% MeOH extract of Allium macrostemon Bunge. The identification and structural elucidation of these compounds were based on their 1D- and 2D-NMR spectra, and HR-FAB-MS data analysis. The isolated compounds were tested for cytotoxicity against four human tumor cell lines in vitro using the sulforhodamine B bioassay.
Selective ring-opening carbonylation of epoxy-steroids
Balazs, Attila,Benedek, Csilla,Szalontai, Gabor,Toroes, Szilard
, p. 271 - 277 (2004)
Ring-opening alkoxycarbonylation of epoxy-steroids has been carried out with a Co2(CO)8/3-hydroxypyridine catalytic system. High chemo- and regioselectivities were obtained under the reaction conditions applied. Structural analysis of the products proved their high stereochemical purity in each case, accompanied by inversion of the original configuration. No carbonylation took place for sterically hindered steranic epoxides.
Stereoselective syntheses of unnatural steroidal C(20R) aldehydes by ionic hydrogenation of C-20 tertiary alcohols
Shingate, Bapurao B.,Hazra, Braja G.,Pore, Vandana S.,Gonnade, Rajesh G.,Bhadbhade, Mohan M.
, p. 9343 - 9347 (2006)
Syntheses of three unnatural steroidal C(20R) aldehydes have been realised from 16-dehydropregnenolone acetate. The salient feature of the synthesis is the ionic hydrogenation of C-20 tertiary alcohols leading to the formation of the C(20R) unnatural isomer with complete stereoselectivity. Oxidative hydrolysis of the dithiane moiety furnished the C(20R) aldehydes.
Stereoselective synthesis and antimicrobial activity of steroidal C-20 tertiary alcohols with thiazole/pyridine side chain
Shingate, Bapurao B.,Hazra, Braja G.,Salunke, Deepak B.,Pore, Vandana S.,Shirazi, Fazal,Deshpande, Mukund V.
, p. 3681 - 3689 (2011)
Stereoselective synthesis of novel steroidal C-20 tertiary alcohols with thiazole and pyridine side chain using Grignard reaction of steroidal ketones and thiazole/pyridine magnesium bromide have been realized. These molecules were evaluated in vitro for their antifungal and antibacterial activities. Most of the compounds exhibited significant antifungal and antibacterial activity against all the tested strains.
Synthesis and Identification of Pregnenolone Derivatives as Inhibitors of Isozymes of 5α-Reductase
Chávez-Riveros, Alejandra,Bratoeff, Eugene,Heuze, Yvonne,Soriano, Juan,Moreno, Isabel,Sánchez-Márquez, Araceli,Cabeza, Marisa
, p. 808 - 816 (2015)
Hyperplasia of the prostate gland and prostate cancer have been associated with high levels of serum 5α-dihydrotestosterone. This steroid is formed from testosterone by the activity of the enzyme 5α-reductase (5α-R) present in the prostate. Thus, inhibition of this enzyme could be a goal for therapies to treat these diseases. This study reports the synthesis and effects of five different 21-esters of pregnenolone derivatives as inhibitors of 5α-R types 1 and 2. The activity of these steroidal compounds was determined using in vivo and in vitro experiments. The results indicate that of the five steroids studied, the 21(p-fluoro)benzoyloxypregna-4,16-diene-3,6,20-trione derivative, whose structure has not yet been reported, has the best molecular conformation to inhibit the in vitro activity of both types of 5α-R. In addition, this steroid also displayed activity in vivo. Apparently, its pharmacological effect was increased by the presence of a keto group at C-6, because this group decreased the possibility that the steroid would be metabolized by hepatic enzymes. In addition, the double bond present at C-4 of this compound also enhanced its inhibitory activity on 5α-R, and the C-21 ester moiety increased its liphophilicity. Therefore, its solubility in the cell membrane and its pharmacological activity were both increased.
Synthesis and evaluation of pyrimidine steroids as antiproliferative agents
Cortés-Percino, Alejandra,Vega-Báez, José Luis,Romero-López, Anabel,Puerta, Adrián,Merino-Montiel, Penélope,Meza-Reyes, Socorro,Padrón, José M.,Montiel-Smith, Sara
, (2019)
A small and focused library of steroidal non-fused and fused pyrimidines was prepared from pregnenolone acetate and diosgenin, respectively. The key step was the cycloaddition reaction of nitrogen-containing 1,3-binucleophiles with the steroidal α,β-unsaturated ketone. Urea, thiourea and guanidine reacted in a similar manner and afforded the steroidal pyrimidines in good yields. The antiproliferative tests against human tumor cell lines gave GI50 values in the micromolar range and had no effect on healthy fibroblasts. Additional experiments indicated that the compounds did not act as P-glycoprotein substrates, thus avoiding the rise of drug resistance. The fused steroidal pyrimidinethione was selected as drug lead for further testing due to its strong antiproliferative activities within the low micromolar range.
Design and synthesis of novel steroidal imidazoles as dual inhibitors of AR/CYP17 for the treatment of prostate cancer
Hou, Qiangqiang,He, Conghui,Lao, Kejing,Luo, Guoshun,You, Qidong,Xiang, Hua
, (2019)
Both AR and CYP17 are important targets for blocking androgen signaling, and it has been accepted that multifunctional drugs have a low risk of drug resistance in the treatment of cancer. Thus, herein a series of steroidal imidazoles were designed, synthesized and evaluated as dual AR/CYP17 ligands. Several compounds displayed good biological profiles in both enzymatic and cellular assays. SAR studies showed that introducing oximino at the C-3 position of steroidal scaffold is beneficial to the enhancement of AR antagonistic activity. Among these compounds, the most potent compound 13a exhibited the best AR inhibition (IC50 = 0.5 μM) that was 27-fold increase compared with the hit compound 5 as well as comparable CYP17 inhibition (IC50 = 11 μM). Additionally, 13a displayed promising anti-proliferative effects on LNCap cell lines with the IC50 value of 23 μM which was superior to positive control Flutamide (IC50 = 28 μM). Furthermore, the docking results of 13a revealed that the oxygen atom at the position of C-3 connected to the heme of CYP17, which may be helpful for its satisfactory dual-target inhibition. In summary, this study provides an efficient strategy for multi-targeting drug discovery in the treatment of prostate cancer.
Steroid-fullerene adducts from Diels-Alder reactions: Characterization and the effect on the activity of Ca2+-ATPase
Li, Lian-Sheng,Hu, Yun-Jin,Wu, Yikang,Wu, Yu-Lin,Yue, Jiachang,Yang, Fuyu
, p. 617 - 621 (2001)
Two new fullerene steroids (1 and 6) have been prepared by the Diels-Alder reaction of silyloxydienes (2 and 3) with [60]fulterene, followed by hydrolysis of the silyl enol ether under acidic conditions. The isolation, characterization, UV-Vis and CD absorption studies of the adducts are presented. A preliminary study on the effect of 1 on sarcoplasmic reticulum (SR) Ca2+-ATPase and survival of human lung adenocarcinoma cancer A549 cells has also been carried out.
