Steroids最新文献

{"title":"Recent advances in the development of 17beta-hydroxysteroid dehydrogenase inhibitors","authors":"Donald Poirier","doi":"10.1016/j.steroids.2024.109529","DOIUrl":"10.1016/j.steroids.2024.109529","url":null,"abstract":"<div><div>The family of 17β-hydroxysteroid dehydrogenases (17β-HSDs) occupies a prominent place due to its number of isoforms, which carry out a bidirectional transformation (reduction of a steroid carbonyl to alcohol and oxidation of a steroid alcohol to ketone) depending on the nature of the cofactor present. Involved in the activation or inactivation of key estrogens and androgens, 17β-HSDs are therefore therapeutic targets whose selective inhibition would make it possible to be considered for the treatment of several diseases, such as breast cancer, prostate cancer, endometriosis, Alzheimer’s disease and osteoporosis. This review article is a continuation of those having reported the great diversity of inhibitors developed over the last years but focusses on inhibitors recently developed. Work to obtain more effective inhibitors that target the first known isoforms (types 1, 2, 3, 5 and 7) has continued, among others, but new inhibitors that target the isoforms more recently reported in the literature (types 10, 12, 13 and 14) are now being reported. Dual inhibitors of two enzymes (17β-HSD1 and steroid sulfatase) were also reported. These inhibitors were grouped according to the 17β-HSD type inhibited and their backbone (steroidal or non-steroidal) when necessary. They were also reported in chronological order and according to the research group.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"213 ","pages":"Article 109529"},"PeriodicalIF":2.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of 13β- and 13α-epimers of 3-hydroxy-17-hydroxymethylestra-1,3,5(10)-triene and considerations on their hormonal and antiproliferative potency","authors":"Yu.V. Kuznetsov ,&nbsp;M.O. Tserfas ,&nbsp;A.M. Scherbakov ,&nbsp;O.E. Andreeva ,&nbsp;D.I. Salnikova ,&nbsp;E.I. Bozhenko ,&nbsp;I.V. Zavarzin ,&nbsp;I.S. Levina","doi":"10.1016/j.steroids.2024.109527","DOIUrl":"10.1016/j.steroids.2024.109527","url":null,"abstract":"<div><div>Starting from 3-methoxyestra-1,3,5(10),16-tetraene-17-carbaldehydes of natural (13β) and epimeric (13α) series, a series of isomeric 3-hydroxy-17-hydroxymethylestra-1,3,5(10)-trienes, including those containing 16α,17α-annulated cyclopropane and cyclohexane ring D’, were prepared using the Corey-Chaykovsky and Diels-Alder reactions followed by reduction-demethylation with diisobutylaluminum hydride and hydrogenation. Target compounds showed antiproliferative effects on MCF-7 breast cancer cells to varying degrees superior to that on MCF-10A cells, in low micromolar concentrations. The <em>ER</em>α<em>-mediated luciferase reporter gene assay</em> demonstrated that obtained steroids without an additional carbocycle or with a cyclopropane 16α,17α-annulated carbocycle are effective <em>ER</em>α activators. In this test, steroids of the natural configuration showed high activity at both 10 nM and 100 nM concentrations, whereas 13α-steroids showed a strong dose-dependent effect, surpassing their natural counterparts at a concentration of 100 nM. The 13β-steroid bearing additional 16α,17α-cyclohexane ring had low activity in the test. A simple docking approach using AutoDock Vina was used as a test for a preliminary assessment of the estrogenicity of the compounds. The scope of its applicability and limitations were shown using examples of synthesized molecules.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109527"},"PeriodicalIF":2.1,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565059","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}

{"title":"Testosterone replacement has a beneficial effect on the hemostatic system by altered gene expression of coagulation factors","authors":"Jafar Vatandoost,&nbsp;Amirreza Yaghoubi-Nezhad,&nbsp;Amir Masoud Sadr,&nbsp;Madjid Momeni-Moghaddam,&nbsp;Toktam Hajjar","doi":"10.1016/j.steroids.2024.109525","DOIUrl":"10.1016/j.steroids.2024.109525","url":null,"abstract":"<div><div>This study aimed to investigate the effects of testosterone replacement therapy on hemostasis and some procoagulant gene expression in mice. 42 mice were randomly divided into two groups of non-orchiectomized (non-ORX) and orchiectomized (ORX) with three subgroups (n = 7) each, were subcutaneously administered with sesame oil (control), 2 and 20 mg/kg/week testosterone enanthate. Orchiectomized mice were allowed to recover for one week before treatment. On the 7th week of treatment, blood samples were collected for coagulation parameters analysis and measurement of plasma testosterone levels. Moreover, quantitative real-time PCR analysis was performed on liver samples to assess the expression of factor IX, factor X, and prothrombin genes. The results showed that supraphysiological doses (20 mg/kg) of testosterone significantly increased plasma testosterone levels in all groups, while physiological doses (2 mg/kg) only increased testosterone levels in non-ORX animals. Although testosterone administration had no effect on prothrombin time (PT) and activated partial thromboplastin time (aPTT), supraphysiological doses reduced bleeding time and clotting time. Furthermore, platelet count increased in a dose-dependent manner with testosterone enanthate treatment. The expression of coagulation factors was also decreased with supraphysiological doses of testosterone. In conclusion, testosterone had significant effects on primary hemostasis and common coagulation pathway, including increased platelet number and aggregation, decreased clotting time, and altered gene expression of coagulation factors.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109525"},"PeriodicalIF":2.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565061","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}

{"title":"Sonogashira coupling-based synthesis and in vitro cytotoxic evaluation of C-2 alkynyl derivatives of withaferin A","authors":"Shabir Ahmad Mir ,&nbsp;Sameera Firdous ,&nbsp;Mir Shahid Maqbool ,&nbsp;Gulzar Hussain ,&nbsp;Mohammad Yaqoob Bhat ,&nbsp;Fayaz A. Malik ,&nbsp;Syed Khalid Yousuf","doi":"10.1016/j.steroids.2024.109526","DOIUrl":"10.1016/j.steroids.2024.109526","url":null,"abstract":"","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109526"},"PeriodicalIF":2.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565057","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}

{"title":"Assessment of anti-cancer evaluation of new metabolites isolated from baked Sarcosphaera crassa: An edible poisonous mushroom","authors":"Zain Ullah ,&nbsp;Mehmet Öztürk","doi":"10.1016/j.steroids.2024.109523","DOIUrl":"10.1016/j.steroids.2024.109523","url":null,"abstract":"<div><div>The growing demand for wild mushrooms as functional foods has increased due to their pharmacological significance. <em>Sarcosphaera crassa</em> is a deadly poisonous mushroom consumed by people living in northern and eastern Europe after being cooked adequately due to its significant properties. Herein, the baked <em>Sarcosphaera crassa</em> was studied for its ingredients. The cytotoxicity of hexane, acetone, and methanol extracts of baked <em>Sarcosphaera crassa</em> was investigated against MCF-7, HT-29, and HeLa cancer cell lines while toxicity against PDF fibroblast healthy cell lines using MTT assay. Acetone and methanol extracts of the baked mushroom exhibited significant cytotoxic activity. Further investigation of cytotoxic extracts afforded three new secondary metabolites, namely, (3<em>β,</em> 22<em>E</em>) ergosta-5, 22-dienyl 3-<em>O</em>-<em>α</em>-yl decanoate (Brassicasteryl decanoate) (<strong>1</strong>), bis (2- ethylpentadecyl) benzene-1,2-dicarboxylate (<strong>2</strong>), and (2<em>S</em>)-4-(aziridine-1-yl)-4-oxobutan-2-yl hexadecanoate (<strong>3</strong>), and six known compounds including ᴅ-sorbitol (<strong>4</strong>), 3<em>β</em>-ergosta-5,22-dien (<strong>5</strong>), two ergosterol-endoperoxides (<strong>6</strong> and <strong>7</strong>), nigerasterol A (<strong>8</strong>) and 5<em>α</em>,9<em>α</em>-epoksiergosta-7,22-dien, 3<em>β</em>,6<em>α</em>-diol (<strong>9</strong>). Among them, <strong>2</strong> exhibited effective cytotoxic activity against MCF-7 (IC₅₀: 33.45 ± 2.9 μg/mL) and HT-29 (IC₅₀: 45.53 ± 0.8 μg/mL) cancer cell lines. Compound <strong>3</strong> demonstrated high activity against HeLa (IC₅₀: 30.45 ± 0.35 μg/mL) and MCF-7 (IC₅₀: 33.55 ± 0.49 μg/mL) cancer cell lines, respectively. On the other hand, compound <strong>1</strong> demonstrated moderate cytotoxic activity against MCF-7 and HT-29 cancer cell lines. Besides, against PDF healthy cell lines, all extracts demonstrated lower toxicity. This discovery highlights the significance of <em>Sarcosphaera crassa</em> as a natural functional food reservoir.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109523"},"PeriodicalIF":2.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547565","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}

{"title":"Invalidating betulinic acid as a potential inhibitor against the main protease of SARS-CoV-2 via combined approaches","authors":"Jiankai Ye ,&nbsp;Tao Xu ,&nbsp;Rui Zhang,&nbsp;Xiaoping Liu,&nbsp;Chao Zhang,&nbsp;Yunyu Chen","doi":"10.1016/j.steroids.2024.109522","DOIUrl":"10.1016/j.steroids.2024.109522","url":null,"abstract":"<div><div>In contrast to an earlier study reporting that betulinic acid is an inhibitor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro), we demonstrated that beutilinic acid is not a potential Mpro inhibitor via combined approaches, including the fluorescence resonance energy transfer (FRET) assay, the fluorescence polarization (FP) assay, and the protease biosensor cleavage assay. Our results suggest that the addition of detergent to the assay buffers is essential for evaluating natural products as Mpro inhibitors. It is necessary to conduct comprehensive testing of Mpro inhibition via combined approaches for antiviral development.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109522"},"PeriodicalIF":2.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475201","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}

{"title":"Expression of pregnenolone-synthesizing enzymes CYP11A1 and CYP1B1 in the human, rat, and mouse brain","authors":"Yiqi Christina Lin,&nbsp;Vassilios Papadopoulos","doi":"10.1016/j.steroids.2024.109521","DOIUrl":"10.1016/j.steroids.2024.109521","url":null,"abstract":"<div><div>The central nervous system (CNS) is capable of synthesizing steroids for modulating essential functions such as neurotransmission, neuroplasticity, and neuroinflammation. These locally synthesized steroids, called neurosteroids, are produced through the conversion of cholesterol into the major steroid precursor pregnenolone, followed by downstream metabolism to form various steroids such as progesterone and allopregnanolone. Given that changes in neurosteroids are implicated in many neurological and psychiatric disorders, understanding the neurosteroidogenesis pathway is crucial. Recent studies have demonstrated an alternative pathway for the biosynthesis of pregnenolone, which is classically produced by CYP11A1 but was found instead to be made by CYP1B1 in human glial cells. However, numerous studies have demonstrated Cyp11a1 expression and activity in rodent brain tissue and brain cells. To elucidate whether species differences exist for the pregnenolone synthesis enzyme in human and rodent brains, we sought to directly compare the expression levels of CYP11A1 and CYP1B1 in human, rat, and mouse CNS tissues. We found that <em>CYP1B1</em> mRNA expression was significantly higher than that of <em>CYP11A1</em> in almost all CNS brain regions in human, rat, and mouse. The exception is in the mouse cerebral cortex, where <em>Cyp11a1</em> RNA was more abundant than <em>Cyp1b1</em>. However, Cyp11a1 protein was clearly detectable in rodent CNS while completely undetectable in human brain. In contrast, the presence of CYP1B1 protein can be observed in both human and rodent brains. These results suggest that CYP1B1 is likely the dominant pregnenolone synthesis enzyme in the human brain, while rodent brains may use both Cyp11a1 and Cyp1b1.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109521"},"PeriodicalIF":2.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441481","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}

{"title":"Current advances in phytosterol free forms and esters: Classification, biosynthesis, chemistry, and detection","authors":"Farid Khallouki ,&nbsp;Wafa Zennouhi ,&nbsp;Lhoussain Hajji ,&nbsp;Mohamed Bourhia ,&nbsp;Laila Benbacer ,&nbsp;Bachir El Bouhali ,&nbsp;Leila Rezig ,&nbsp;Marc Poirot ,&nbsp;Gérard Lizard","doi":"10.1016/j.steroids.2024.109520","DOIUrl":"10.1016/j.steroids.2024.109520","url":null,"abstract":"<div><div>Phytosterols are plant sterols that are important secondary plant metabolites with significant pharmacological properties. Their presence in the plant kingdom concerns many unrelated botanical families such as oleageneous plants and cereals. The structures of phytosterols evoke those of cholesterol. These molecules are composed of a sterane ring, also known as perhydrocyclopentanophenanthrene, along with a methyl or ethyl group at C-24 in their side chains, a hydroxyl group at C-3 on ring A, and one or two double bonds in the B ring. Phytosterols display different oxidation degrees at the sterane ring and at the side chain as well as varying numbers of carbons with complex stereochemistries. Fats and water solubilities of phytosterols have been achieved by physical, chemical and enzymatic esterifications to favor their bioavailability and to improve the sensory quality of food, and the efficiency of pharmaceutic and cosmetic products. This review aims to provide comprehensive information starting from the definition and structural classification of phytosterols, and exposes an update of their biogenic relationships. Next, the synthesis of phytosterol esters and their applications as well as their effective roles as hormone precursors are discussed. Finally, a concise exploration of the latest advancements in phytosterol / oxyphytosterols analysis techniques is provided, with a particular focus on modern hyphenated techniques.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109520"},"PeriodicalIF":2.1,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393486","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}

{"title":"A sustainable approach towards extraction of diosgenin from fenugreek seeds using polystyrene/divinyl benzene resin","authors":"Sharavan Kumar ,&nbsp;B.M. Praveen ,&nbsp;Aralihalli Sudhakara","doi":"10.1016/j.steroids.2024.109519","DOIUrl":"10.1016/j.steroids.2024.109519","url":null,"abstract":"<div><div>Diosgenin, a bioactive molecule; is one of the deeply explored saponin with a wide spectrum of benefits against various ailments. The extraction and yield enhancement of diosgenin from a wide range of naturally occurring medicinal products has always been a challenging task for its commercial usage. The current research work envisages the use of a novel resin to maximize the yield of diosgenin. The extracted diosgenin was characterized using modern techniques. The current method qualifies for the extraction of diosgenin at a large scale making it a commercially viable technique.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109519"},"PeriodicalIF":2.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368195","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}

{"title":"An efficient regioconvergent synthesis of 3-aza-obeticholic acid","authors":"Lawrence D. Harris ,&nbsp;Roselis A. Landaeta Aponte ,&nbsp;Wanting Jiao ,&nbsp;Scott A. Cameron ,&nbsp;Alex Weymouth-Wilson ,&nbsp;Richard H. Furneaux ,&nbsp;Benjamin J. Compton ,&nbsp;Andreas Luxenburger","doi":"10.1016/j.steroids.2024.109517","DOIUrl":"10.1016/j.steroids.2024.109517","url":null,"abstract":"<div><div>Bile acids (BAs) are steroidal molecules that play important roles in nutrient absorption, distribution, and excretion. They also act on specific receptors implicated in various metabolic and inflammatory diseases demonstrating their importance as potential drug candidates. Accordingly, there has been a concerted effort to develop new BA derivatives to probe structure–activity relationships with the goal of discovering BA analogues with enhanced pharmacological properties. Among the many steroidal derivatisations reported, the formation of endocyclic azasteroids appeals due to their potential to deliver altered biological responses with minimal change to the steroidal superstructure. Here, we report the synthesis of 3-aza-obeticholic acid (<strong>6</strong>) <em>via</em> a regioconvergent route. Ammoniolysis of lactones, formed from an <em>m</em>-CPBA-mediated Baeyer-Villiger reaction on a 3-keto-OCA derivative, furnished protected intermediate amido-alcohols which were separately elaborated to amino-alcohols <em>via</em> Hofmann degradation with BAIB. Upon individual <em>N</em>-Boc-protection, these underwent annulation to the 3-aza-A-ring when subjected to either mesylation or a Dess-Martin oxidation/hydrogenation sequence. Global deprotection of the 3-aza-intermediate delivered 3-aza-OCA in ten steps and an overall yield of up to 19%.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109517"},"PeriodicalIF":2.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}