Steroids最新文献_第8页

Corrigendum to “Effects of neural-derived estradiol on actin polymerization and synaptic plasticity-related proteins in prefrontal and hippocampal cells of mice” [Steroids 177 (2022) 108935] 更正："神经源性雌二醇对小鼠前额叶和海马细胞肌动蛋白聚合和突触可塑性相关蛋白的影响" [Steroids 177 (2022) 108935]。

IF 2.1 4区医学

Steroids Pub Date : 2024-07-27 DOI: 10.1016/j.steroids.2024.109473

Yu Feng, Rengfei Shi, Jingyun Hu, Shujie Lou

引用次数: 0

Steroidal 21-imidazolium salt derivatives: Synthesis and anticancer activity 甾体 21-咪唑盐衍生物：合成与抗癌活性

IF 2.1 4区医学

Steroids Pub Date : 2024-07-26 DOI: 10.1016/j.steroids.2024.109475

Natalia S. Sucman , Dmitri Ya. Bilan , Sergiu V. Cojocari , Vsevolod S. Pogrebnoi , Eugenia P. Stîngaci , Vladimir A. Khripach , Vladimir N. Zhabinskii , Tatsiana V. Tsybruk , Irina P. Grabovec , Olesya V. Panibrat , Leentje Persoons , Dominique Schols , Mathy Froeyen , Sergiu Shova , Steven De Jonghe , Fliur Z. Macaev

{"title":"Steroidal 21-imidazolium salt derivatives: Synthesis and anticancer activity","authors":"Natalia S. Sucman , Dmitri Ya. Bilan , Sergiu V. Cojocari , Vsevolod S. Pogrebnoi , Eugenia P. Stîngaci , Vladimir A. Khripach , Vladimir N. Zhabinskii , Tatsiana V. Tsybruk , Irina P. Grabovec , Olesya V. Panibrat , Leentje Persoons , Dominique Schols , Mathy Froeyen , Sergiu Shova , Steven De Jonghe , Fliur Z. Macaev","doi":"10.1016/j.steroids.2024.109475","DOIUrl":"10.1016/j.steroids.2024.109475","url":null,"abstract":"<div><p>Nitrogen-containing steroids are known as prostate cancer therapeutics. In this work, a series of pregnane derivatives bearing an imidazolium moiety were synthesized using Δ<sup>16</sup>-20-ketones as starting material. An improved approach for the construction of the 20-keto-21-heterocycle-substituted fragment involved the rearrangement of 16,17-epoxides with HCl, followed by reaction of the formed α-chloroketone with 1-substituted imidazoles. Binding affinity analysis of the imidazolium steroids and their synthetic intermediates to human CYP17A1 showed only type I (substrate-like) interactions. The strongest affinity was observed for 16α,17α-epoxy-5α-pregnan-20-on-3β-ol (K<sub>d</sub> = 0.66 ± 0.05 µM). The steroid derivatives have been evaluated for antitumor activity against a range of prostate cancer cells as well as against various other solid tumor and hematologic cancer cell lines. All 21-imidazolium salts were active against the hormone-dependent prostate cancer line LNCaP. The most pronounced cytotoxicity in solid tumor and hematologic cancer cell lines was observed for intermediate product, 21-chloro-5α-pregn-16-en-20-on-3β-ol. Among the imidazolium salts, the derivatives with a single bond were more cytotoxic than their unsaturated congeners.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"210 ","pages":"Article 109475"},"PeriodicalIF":2.1,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Steroid sulfatase in mouse liver and testis: Characterization, ontogeny and localization 小鼠肝脏和睾丸中的类固醇硫酸酯酶：特征、本体和定位。

IF 2.1 4区医学

Steroids Pub Date : 2024-07-23 DOI: 10.1016/j.steroids.2024.109483

Barathi Balasubramonian, Kyle W. Selcer

{"title":"Steroid sulfatase in mouse liver and testis: Characterization, ontogeny and localization","authors":"Barathi Balasubramonian, Kyle W. Selcer","doi":"10.1016/j.steroids.2024.109483","DOIUrl":"10.1016/j.steroids.2024.109483","url":null,"abstract":"<div><p>Steroid hormones often circulate in the plasma as inactive sulfated forms, such as estrone sulfate and dehydroepiandrosterone sulfate. The enzyme steroid sulfatase (STS) converts these steroids into active forms, mainly estrogens, in peripheral tissues. STS is present in most tissues, but it occurs at higher levels in certain organs, notably liver and placenta. In this study, we examined the tissue distribution of STS in a prominent laboratory model, the house mouse (<em>Mus musculus)</em>. Tissues included were heart, liver, small intestine, skeletal muscle, and gonads of both sexes. An <sup>3</sup>H-estrone-sulfate conversion assay was used to measure STS activity in tissue homogenates and extracts. STS activities were high for hepatic tissue homogenates of both genders. Testicular STS levels were similar to those of liver, while STS activities of ovary, small intestine, heart, and muscle were considerably lower. The specific STS inhibitors, EMATE and STX-64 virtually eliminated STS activity in hepatic microsomes and cytosols, verifying that the observed enzyme activity was due to STS. Enzyme kinetic assays showed Km values of 8.6 µM for liver and 9.1 µM for testis, using E<sub>1</sub>S as substrate. Hepatic and testicular STS activities, measured in CHAPS-extracted microsome, were low up to 5 weeks of age and were higher through 56 weeks. Western blotting, with a specific STS antibody, confirmed the presence of STS protein (65 Da) in both liver and testis. Immunofluorescence of tissue sections detected the presence of STS protein in hepatocytes, in testicular Leydig cells and in seminiferous tubules (Leydig cells and developing germ cells). These results suggest that STS may have a significant role in testicular function.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"210 ","pages":"Article 109483"},"PeriodicalIF":2.1,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibitors of the transactivation domain of androgen receptor as a therapy for prostate cancer 将雄激素受体转录激活结构域抑制剂作为前列腺癌疗法。

IF 2.1 4区医学

Steroids Pub Date : 2024-07-23 DOI: 10.1016/j.steroids.2024.109482

Jon K. Obst, Amy H. Tien, Josie C. Setiawan, Lauren F. Deneault, Marianne D. Sadar

{"title":"Inhibitors of the transactivation domain of androgen receptor as a therapy for prostate cancer","authors":"Jon K. Obst, Amy H. Tien, Josie C. Setiawan, Lauren F. Deneault, Marianne D. Sadar","doi":"10.1016/j.steroids.2024.109482","DOIUrl":"10.1016/j.steroids.2024.109482","url":null,"abstract":"<div><p>The androgen receptor (AR) is a modular transcription factor which functions as a master regulator of gene expression. AR protein is composed of three functional domains; the ligand-binding domain (LBD); DNA-binding domain (DBD); and the intrinsically disordered <em>N</em>-terminal transactivation domain (TAD). AR is transactivated upon binding to the male sex hormone testosterone and other androgens. While the AR may tolerate loss of its LBD, the TAD contains activation function-1 (AF-1) that is essential for all AR transcriptional activity. AR is frequently over-expressed in most prostate cancer. Currently, androgen deprivation therapy (ADT) in the form of surgical or chemical castration remains the standard of care for patients with high risk localized disease, advanced and metastatic disease, and those patients that experience biochemical relapse following definitive primary treatment. Patients with recurrent disease that receive ADT will ultimately progress to lethal metastatic castration-resistant prostate cancer. In addition to ADT not providing a cure, it is associated with numerous adverse effects including cardiovascular disease, osteoporosis and sexual dysfunction. Recently there has been a renewed interest in investigating the possibility of using antiandrogens which competitively bind the AR-LBD without ADT for patients with hormone sensitive, non-metastatic prostate cancer. Here we describe a class of compounds termed AR transactivation domain inhibitors (ARTADI) and their mechanism of action. These compounds bind to the AR-TAD to inhibit AR transcriptional activity in the absence and presence of androgens. Thus these inhibitors may have utility in preventing prostate cancer growth in the non-castrate setting.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"210 ","pages":"Article 109482"},"PeriodicalIF":2.1,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antitumor progestins activity: Cytostatic effect and immune response 抗肿瘤孕激素活性：细胞抑制作用和免疫反应

IF 2.1 4区医学

Steroids Pub Date : 2024-07-22 DOI: 10.1016/j.steroids.2024.109474

T. Pavlik , E. Konchekov , N. Shimanovskii

引用次数: 0

The role of cardiac surgery and interventional cardiology in addressing cardiovascular risks associated with anabolic steroid use 心脏外科和介入心脏病学在应对与使用合成类固醇有关的心血管风险方面的作用。

IF 2.1 4区医学

Steroids Pub Date : 2024-07-18 DOI: 10.1016/j.steroids.2024.109472

Ignazio Condello, Giuseppe Nasso

引用次数: 0

Synthesis and comparative analysis of the cytotoxicity and mitochondrial effects of triphenylphosphonium and F16 maslinic and corosolic acid hybrid derivatives 三苯基膦和 F16 马斯林酸及科罗索酸杂交衍生物的合成及其细胞毒性和线粒体效应的比较分析。

IF 2.1 4区医学

Steroids Pub Date : 2024-07-11 DOI: 10.1016/j.steroids.2024.109471

Anna Yu. Spivak , Ulyana Sh. Kuzmina , Darya A. Nedopekina , Mikhail V. Dubinin , Rezeda R. Khalitova , Eldar V. Davletshin , Yulia V. Vakhitova , Konstantin N. Belosludtsev , Vener A. Vakhitov

{"title":"Synthesis and comparative analysis of the cytotoxicity and mitochondrial effects of triphenylphosphonium and F16 maslinic and corosolic acid hybrid derivatives","authors":"Anna Yu. Spivak , Ulyana Sh. Kuzmina , Darya A. Nedopekina , Mikhail V. Dubinin , Rezeda R. Khalitova , Eldar V. Davletshin , Yulia V. Vakhitova , Konstantin N. Belosludtsev , Vener A. Vakhitov","doi":"10.1016/j.steroids.2024.109471","DOIUrl":"10.1016/j.steroids.2024.109471","url":null,"abstract":"<div><p>The cytotoxic profile and antiproliferative and mitochondrial effects of triterpene acid conjugates with mitochondriotropic lipophilic triphenylphosphonium (TPP<sup>+</sup>) and F16 cations were evaluated. Maslinic and corosolic acids chosen as the investigation objects were synthesized from commercially available oleanolic and ursolic acids. Study of the cytotoxic activity of TPP<sup>+</sup> and F16 triterpenoid derivatives against six tumor cell lines demonstrated a comparable synergistic effect in the anticancer activity, which was most pronounced in the case of MCF-7 mammary adenocarcinoma cells and Jurkat and THP-1 leukemia cells. The corosolic and maslinic acid hybrid derivatives caused changes in the progression of tumor cell cycle phases when present in much lower doses than their natural triterpene acid precursors. The treatment of tumor cell lines with the conjugates resulted in the cell cycle arrest in the G1 phase and increase in the cell population in the subG1 phase. The cationic derivatives of the acids were markedly superior to their precursors as inducers of hyperproduction of reactive oxygen species and more effectively decreased the mitochondrial potential in isolated rat liver mitochondria. We concluded that the observed cytotoxic effect of TPP<sup>+</sup> and F16 triterpenoid conjugates is attributable to the ability of these compounds to initiate mitochondrial dysfunctions. Their cytotoxicity, antiproliferative action, and mitochondrial effects depend little on the type of cationic groups used.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"209 ","pages":"Article 109471"},"PeriodicalIF":2.1,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Practical synthesis of chenodeoxycholic acid from phocaecholic acid 从 phocaecholic acid 中实际合成 chenodeoxycholic acid。

IF 2.1 4区医学

Steroids Pub Date : 2024-07-10 DOI: 10.1016/j.steroids.2024.109470

引用次数: 0

Synthesis and anticancer properties of a hybrid molecule with the testosterone and estradiol head-groups 具有睾酮和雌二醇头基的混合分子的合成和抗癌特性。

IF 2.1 4区医学

Steroids Pub Date : 2024-07-09 DOI: 10.1016/j.steroids.2024.109469

Alexis Paquin , Fayanne Nolin , Chahrazed Bouzriba , Sébastien Fortin , Irina F. Sevrioukova , Gervais Bérubé

{"title":"Synthesis and anticancer properties of a hybrid molecule with the testosterone and estradiol head-groups","authors":"Alexis Paquin , Fayanne Nolin , Chahrazed Bouzriba , Sébastien Fortin , Irina F. Sevrioukova , Gervais Bérubé","doi":"10.1016/j.steroids.2024.109469","DOIUrl":"10.1016/j.steroids.2024.109469","url":null,"abstract":"<div><p>This is the first report on a unique hybrid molecule made of estradiol and testosterone (TS). This distinctive hybrid molecule (<strong>1</strong>) was designed to interact with both the estrogen receptor (ER) and the androgen receptor (AR) found in hormone-dependent female and male cancer cells, and was synthesized using ethynylestradiol (17EE) as the estrogenic component and 7α-(4-azido-but-2-enyl)-4-androsten-17β-ol-3-one as the androgenic counterpart in a seven-step reaction with ∼ 26 % overall yield. We reasoned that the dual receptor binding ability could allow <strong>1</strong> to act as an antihormone. This was tested on hormone-dependent and hormone-independent breast cancer (BCa) and prostate cancer (PCa) cells. The antiproliferative activity was also assessed on colon and skin cancer cells. We found that <strong>1</strong> was active against MCF7 (ER + ) BCa cells (IC<sub>50</sub> of 4.9 μM), had lower inhibitory potency on LNCaP (AR + ) PCa cells (IC<sub>50</sub> > 5 μM) and no effect on PC3 and DU145 (AR-) PCa cells. This suggests that the estrogenic component of <strong>1</strong> can interact with the ER on MCF7 cells more effectively than the androgenic component with the AR on LNCaP PCa cells, possibly due to a suboptimal spacer or linkage site(s). Nonetheless, the hybrid <strong>1</strong> was active against colon (HT-29) and melanoma (M21) cancer cells (IC<sub>50</sub> of 3.5 μM and 2.3 μM, respectively), and had low cross-reactivity with the drug- and androgen-metabolizing cytochrome P450 3A4 (CYP3A4, IC<sub>50</sub> ≫ 5 µM). These findings demonstrate the anticancer potential of <strong>1</strong> and warrant further explorations on this new type of hybrids.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"209 ","pages":"Article 109469"},"PeriodicalIF":2.1,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the therapeutic potential of steroidal alkaloids in managing Alzheimer’s disease 探索甾体生物碱治疗阿尔茨海默病的潜力。

IF 2.1 4区医学

Steroids Pub Date : 2024-07-02 DOI: 10.1016/j.steroids.2024.109468

Pratima P. Pandey, Maushmi S. Kumar

{"title":"Exploring the therapeutic potential of steroidal alkaloids in managing Alzheimer’s disease","authors":"Pratima P. Pandey, Maushmi S. Kumar","doi":"10.1016/j.steroids.2024.109468","DOIUrl":"10.1016/j.steroids.2024.109468","url":null,"abstract":"<div><p>Steroidal alkaloids are secondary metabolites that are often found in plants, fungi and sponges. These compounds are considered as a source of bioactive compounds for the treatment of chronic diseases, such as neurological disorder like Alzheimer’s disease (AD). Some examples of alkaloid derivatives currently used to treat AD symptoms include galantamine, huperzine A, and other alkaloids. AD is a multifactorial disease caused by multiple factors such as inflammation, oxidative stress, and protein aggregation. Based on the various important neuroprotective activities and different pharmacological effects of steroidal alkaloids with polypharmacological modulatory effects, they can lead to the development of new drugs for the treatment of AD. There are limited studies on the involvement of steroidal alkaloids in AD. Therefore, the mechanisms and neuroprotective abilities of these compounds are still poorly understood. The purpose of this review article is to provide an overview of the mechanism, toxicity and neuroprotective benefits of steroidal alkaloids and to discuss future possibilities to improve the application of steroidal alkaloids as anti-AD agents. The therapeutic value and limitations of the steroidal alkaloid are investigated to provide new perspectives for future clinical development studies.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"209 ","pages":"Article 109468"},"PeriodicalIF":2.1,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0