Pub Date : 2025-06-02DOI: 10.1016/j.steroids.2025.109640
Bu-Luan Liang , Yan-Xin Yue , De-Jie Zhang , Hao-Jie Ni , Xiang-Zhong Gu , Wen-Wei Qiu , Chen-Chen Li
25-Hydroxycholesterol not only exhibits various important biological activities but also plays a crucial role in the synthesis of 25-hydroxyvitamin D3. To date, researchers have proposed multiple synthetic routes for 25-hydroxycholesterol. Herein, a novel synthetic method for 25-hydroxycholesterol is described, involving a seven-step reaction that starts from economical and commercially available plant-derived bisnoralcohol, with an overall yield of up to 43.4%. Key reaction conditions, including solvents, reaction temperatures, bases and catalysts, were thoroughly investigated and optimized. This novel synthetic route provides a cost-effective strategy for the potential large-scale production of plant-derived 25-hydroxycholesterol.
{"title":"Synthesis of 25-hydroxycholesterol from bisnoralcohol","authors":"Bu-Luan Liang , Yan-Xin Yue , De-Jie Zhang , Hao-Jie Ni , Xiang-Zhong Gu , Wen-Wei Qiu , Chen-Chen Li","doi":"10.1016/j.steroids.2025.109640","DOIUrl":"10.1016/j.steroids.2025.109640","url":null,"abstract":"<div><div>25-Hydroxycholesterol not only exhibits various important biological activities but also plays a crucial role in the synthesis of 25-hydroxyvitamin D<sub>3</sub>. To date, researchers have proposed multiple synthetic routes for 25-hydroxycholesterol. Herein, a novel synthetic method for 25-hydroxycholesterol is described, involving a seven-step reaction that starts from economical and commercially available plant-derived bisnoralcohol, with an overall yield of up to 43.4%. Key reaction conditions, including solvents, reaction temperatures, bases and catalysts, were thoroughly investigated and optimized. This novel synthetic route provides a cost-effective strategy for the potential large-scale production of plant-derived 25-hydroxycholesterol.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"221 ","pages":"Article 109640"},"PeriodicalIF":2.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144213488","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}
Etomidate, a general anaesthetic, is known to possess inhibitory activity on steroid 11β-hydroxylase at subanaesthetic concentrations. An emerging trend of abuse of etomidate as well as its analogues propoxate/isopropoxate has recently been observed. Their effects on adrenal steroidogenesis as drugs of abuse remain to be elucidated. Steroid excretion patterns of etomidate and propoxate/isopropoxate users were analysed for evidence of disrupted steroidogenesis.
Method
This is a retrospective, cross-sectional study. Urine steroid profiling by gas chromatography-mass spectrometry-based method was performed on spot urine specimens positive for etomidate, propoxate/isopropoxate and/or their metabolites by liquid chromatography-tandem mass spectrometry. Results were compared with routine clinical specimens with normal adult (≥ 18 years of age) urine steroid profiles, analysed between 1st January 2022 and 24th June 2024. Additional clinical and biochemical data were retrieved from the electronic patient records for review.
Results
Ten male and ten female adult users, aged 18 to 54 years, were included in this study. Their steroid excretion patterns were compared against 377 normal profiles. Hypokalaemia and concomitant drugs of abuse were present in the majority of cases. Psychiatric symptoms were noted in eight out of 20 cases. Multiple metabolites, including tetrahydro-11-deoxycortisol, tetrahydro-deoxycorticosterone and multiple adrenal androgen metabolites, were elevated in etomidate and propoxate/isopropoxate abusers. The pattern indicates 11β-hydroxylase inhibition.
Conclusion
11β-hydroxylase inhibition was demonstrated in recreational users of etomidate and/or its analogues, explaining the clinical features of hypokalaemia, and hyperandrogenism in female patients. Misuse of the compounds could be a harbinger of an increasing prevalence of acquired 11β-hydroxylase deficiency.
{"title":"Acquired 11β-Hydroxylase deficiency in etomidate and (Iso)propoxate abusers: A nascent endocrine condition","authors":"Yee-Ting Cheung , Choi-Yee Lau , Jeremiah Sik-Bit Tseung , Kelvin Yat-Chung Yu , Hoi-Ning Cheung , Chi-Chung Shek , Pak-Lam Sammy Chen , Yeow-Kuan Chong","doi":"10.1016/j.steroids.2025.109639","DOIUrl":"10.1016/j.steroids.2025.109639","url":null,"abstract":"<div><h3>Background</h3><div>Etomidate, a general anaesthetic, is known to possess inhibitory activity on steroid 11β-hydroxylase at subanaesthetic concentrations. An emerging trend of abuse of etomidate as well as its analogues propoxate/isopropoxate has recently been observed. Their effects on adrenal steroidogenesis as drugs of abuse remain to be elucidated. Steroid excretion patterns of etomidate and propoxate/isopropoxate users were analysed for evidence of disrupted steroidogenesis.</div></div><div><h3>Method</h3><div>This is a retrospective, cross-sectional study. Urine steroid profiling by gas chromatography-mass spectrometry-based method was performed on spot urine specimens positive for etomidate, propoxate/isopropoxate and/or their metabolites by liquid chromatography-tandem mass spectrometry. Results were compared with routine clinical specimens with normal adult (≥ 18 years of age) urine steroid profiles, analysed between 1st January 2022 and 24th June 2024. Additional clinical and biochemical data were retrieved from the electronic patient records for review.</div></div><div><h3>Results</h3><div>Ten male and ten female adult users, aged 18 to 54 years, were included in this study. Their steroid excretion patterns were compared against 377 normal profiles. Hypokalaemia and concomitant drugs of abuse were present in the majority of cases. Psychiatric symptoms were noted in eight out of 20 cases. Multiple metabolites, including tetrahydro-11-deoxycortisol, tetrahydro-deoxycorticosterone and multiple adrenal androgen metabolites, were elevated in etomidate and propoxate/isopropoxate abusers. The pattern indicates 11β-hydroxylase inhibition.</div></div><div><h3>Conclusion</h3><div>11β-hydroxylase inhibition was demonstrated in recreational users of etomidate and/or its analogues, explaining the clinical features of hypokalaemia, and hyperandrogenism in female patients. Misuse of the compounds could be a harbinger of an increasing prevalence of acquired 11β-hydroxylase deficiency.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"220 ","pages":"Article 109639"},"PeriodicalIF":2.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189279","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}
Daidzein, a soy-derived phytoestrogen, administered directly in the heart does not show cardioprotective effects against myocardial ischemia–reperfusion (IR) in isolated rat hearts. This study aimed to investigate whether cardioprotective effects of enteral daidzein against myocardial IR are promoted by equol, a metabolite of daidzein, through phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway.
Methods
Two experiments involving the Langendorff system were performed. During experiment 1, rats were divided into: daidzein group received 100 mg/kg of daidzein and control group received saline enterally 24 h before heart excision. After the rats were euthanized, blood samples were obtained to measure equol levels. Hearts were perfused with modified Krebs-Henseleit (KH) buffer before and after no-flow ischemia. During experiment 2, rats were divided into daidzein + WT (wortmannin) and control + WT groups, where daidzein (100 mg/kg) or saline (control + WT) was administered enterally 24 h before heart excision. To assess the role of the PI3K/Akt signaling pathway, an inhibitor of PI3K (wortmannin) was administered before and after no-flow ischemia in both groups. The primary outcome was the maximum left ventricular pressure derivative (LV dP/dt max) after reperfusion.
Results
LV dP/dt max values of the daidzein group at 10, 15, and 20 min after reperfusion were significantly higher than those of the control group (P < 0.05). This effect was diminished by wortmannin. Enteral daidzein significantly increased serum equol levels (daidzein group: 541.5 ± 330.8 nmol/L; control group: 140.6 ± 43.3 nmol/L; P = 0.0043).
Conclusion
Enteral daidzein exhibited cardioprotective effects via PI3K/Akt signaling pathway activation, probably induced by increased serum equol level.
{"title":"Roles of equol and the PI3K/Akt signaling pathway in the cardioprotective effects of enteral daidzein against ischemia–reperfusion injury in isolated rat hearts","authors":"Mariko Yamada , Keisuke Omiya , Yosuke Nakadate , Takeshi Oguchi , Masako Abe , Akiko Kawakami , Takashi Matsukawa","doi":"10.1016/j.steroids.2025.109637","DOIUrl":"10.1016/j.steroids.2025.109637","url":null,"abstract":"<div><h3>Purpose</h3><div>Daidzein, a soy-derived phytoestrogen, administered directly in the heart does not show cardioprotective effects against myocardial ischemia–reperfusion (IR) in isolated rat hearts. This study aimed to investigate whether cardioprotective effects of enteral daidzein against myocardial IR are promoted by equol, a metabolite of daidzein, through phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway.</div></div><div><h3>Methods</h3><div>Two experiments involving the Langendorff system were performed. During experiment 1, rats were divided into: daidzein group received 100 mg/kg of daidzein and control group received saline enterally 24 h before heart excision. After the rats were euthanized, blood samples were obtained to measure equol levels. Hearts were perfused with modified Krebs-Henseleit (KH) buffer before and after no-flow ischemia. During experiment 2, rats were divided into daidzein + WT (wortmannin) and control + WT groups, where daidzein (100 mg/kg) or saline (control + WT) was administered enterally 24 h before heart excision. To assess the role of the PI3K/Akt signaling pathway, an inhibitor of PI3K (wortmannin) was administered before and after no-flow ischemia in both groups. The primary outcome was the maximum left ventricular pressure derivative (LV dP/dt max) after reperfusion.</div></div><div><h3>Results</h3><div>LV dP/dt max values of the daidzein group at 10, 15, and 20 min after reperfusion were significantly higher than those of the control group (<em>P</em> < 0.05). This effect was diminished by wortmannin. Enteral daidzein significantly increased serum equol levels (daidzein group: 541.5 ± 330.8 nmol/L; control group: 140.6 ± 43.3 nmol/L; <em>P</em> = 0.0043).</div></div><div><h3>Conclusion</h3><div>Enteral daidzein exhibited cardioprotective effects via PI3K/Akt signaling pathway activation, probably induced by increased serum equol level.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"220 ","pages":"Article 109637"},"PeriodicalIF":2.1,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125250","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}
Pub Date : 2025-05-21DOI: 10.1016/j.steroids.2025.109638
Sergey A. Popov , Elvira E. Shults , Dmitry S. Baev , Varvara Yu. Chirkova , Ekaterina A. Volosnikova , Svetlana V. Belenkaya , Dmitry N. Shcherbakov , Mikhail.A. Pokrovsky , Mohammad S. Hamad , Andrey G. Pokrovsky
A series of new heterocyclic ursane and 28-norursane hybrids − derivatives of 5-amino-1,2,3,4-thiatriazole, 1-tetrazole–5-thione, and 1-tetrazole–5-amines were prepared. Reacting triterpenoids holding NCS groups at different distances from the pentacyclic backbone with hydrazine hydrate resulted in ursane-derived hydrazinecarbothioamides. Subsequent nitrosation afforded terpenoid derivatives of 5-amino-1,2,3,4-thiatriazole. Heterocyclization of amino-thioureas with 3β-acetoxyurs-12-en-28-yl substituent under the action of Hg(OAc)2-NaN3 led to hybrids of 1-tetrazole–5-amines. 1-Tetrazole–5-thiones with different positions of heterocycle relative to the triterpene skeleton were prepared by coupling sodium azide with triterpene isothiocyanates. The activity of the new heterocyclic derivatives as inhibitors of 3CLpro of SARS-CoV-2 was investigated. Remarkable inhibition was observed for the 1-tetrazole-5-thione hybrids of triterpenoids. The highest activity among the studied compounds was provided by the combination of a 1-tetrazole-5-thione moiety at the C(28)H2 group of the ursane frame having a free OH group at the 3-position. Molecular docking assumed the covalent binding of 3CLpro via the formation of a disulfide bond between the thiol groups of the catalytic Cys145 and the tetrazole heterocycle of the new hybrid compounds. The triterpenoid backbone provided multiple external hydrophobic contacts essential for the stability of the complex. The results demonstrate the potential of heterocyclic thione hybrids as non-peptidomimetic covalent inhibitors targeting 3CLpro protease (3-Chymotrypsin-like Protease).
{"title":"Ursane hybrids with 5-amino-1,2,3,4-thiatriazole, 1-tetrazole-5-thione, and 1-tetrazole-5-amines and study of their inhibition of main SARS-CoV-2 protease","authors":"Sergey A. Popov , Elvira E. Shults , Dmitry S. Baev , Varvara Yu. Chirkova , Ekaterina A. Volosnikova , Svetlana V. Belenkaya , Dmitry N. Shcherbakov , Mikhail.A. Pokrovsky , Mohammad S. Hamad , Andrey G. Pokrovsky","doi":"10.1016/j.steroids.2025.109638","DOIUrl":"10.1016/j.steroids.2025.109638","url":null,"abstract":"<div><div>A series of new heterocyclic ursane and 28-norursane hybrids − derivatives of 5-amino-1,2,3,4-thiatriazole, 1-tetrazole–5-thione, and 1-tetrazole–5-amines were prepared. Reacting triterpenoids holding <img>N<img>C<img>S groups at different distances from the pentacyclic backbone with hydrazine hydrate resulted in ursane-derived hydrazinecarbothioamides. Subsequent nitrosation afforded terpenoid derivatives of 5-amino-1,2,3,4-thiatriazole. Heterocyclization of amino-thioureas with 3β-acetoxyurs-12-en-28-yl substituent under the action of Hg(OAc)<sub>2</sub>-NaN<sub>3</sub> led to hybrids of 1-tetrazole–5-amines. 1-Tetrazole–5-thiones with different positions of heterocycle relative to the triterpene skeleton were prepared by coupling sodium azide with triterpene isothiocyanates. The activity of the new heterocyclic derivatives as inhibitors of 3CLpro of SARS-CoV-2 was investigated. Remarkable inhibition was observed for the 1-tetrazole-5-thione hybrids of triterpenoids. The highest activity among the studied compounds was provided by the combination of a 1-tetrazole-5-thione moiety at the C(28)H<sub>2</sub> group of the ursane frame having a free OH group at the 3-position. Molecular docking assumed the covalent binding of 3CLpro via the formation of a disulfide bond between the thiol groups of the catalytic Cys145 and the tetrazole heterocycle of the new hybrid compounds. The triterpenoid backbone provided multiple external hydrophobic contacts essential for the stability of the complex. The results demonstrate the potential of heterocyclic thione hybrids as non-peptidomimetic covalent inhibitors targeting 3CLpro protease (3-Chymotrypsin-like Protease).</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"220 ","pages":"Article 109638"},"PeriodicalIF":2.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133110","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}
Pub Date : 2025-05-19DOI: 10.1016/j.steroids.2025.109629
Jiacheng Weng , Siqi Li , Runchao Ma, Qi Shi, Xiongyu Meng, Guifen Zhou, Luping Qin, Huaqiang Li
A new 18,22-cyclosterol, aspersteroline A (1), and a new DMOA-derived meroterpenoid, asperterpene O (2), along with three known compounds (3 − 5), namely mer-NF8054X (3), terretonin D (4), and asperterpene J (5), were isolated from the soil-derived Aspergillus versicolor QC812. The structures of new compounds were established based on widespread spectrographic methods, mainly including 1D & 2D NMR and HRESIMS analyses, and the absolute configurations were further confirmed by comparison of calculated and experimental electronic circular dichroism (ECD) curves. The cytotoxicity of isolates was evaluated on five human tumor cell lines, 1 and 3 showed moderate cytotoxic activities against HL-60.
{"title":"New secondary metabolites from the soil-derived Aspergillus versicolor QC812","authors":"Jiacheng Weng , Siqi Li , Runchao Ma, Qi Shi, Xiongyu Meng, Guifen Zhou, Luping Qin, Huaqiang Li","doi":"10.1016/j.steroids.2025.109629","DOIUrl":"10.1016/j.steroids.2025.109629","url":null,"abstract":"<div><div>A new 18,22-cyclosterol, aspersteroline A (<strong>1</strong>), and a new DMOA-derived meroterpenoid, asperterpene O (<strong>2</strong>), along with three known compounds (<strong>3</strong> − <strong>5</strong>), namely <em>mer</em>-NF8054X (<strong>3</strong>), terretonin D (<strong>4</strong>), and asperterpene J (<strong>5</strong>), were isolated from the soil-derived <em>Aspergillus versicolor</em> QC812. The structures of new compounds were established based on widespread spectrographic methods, mainly including 1D & 2D NMR and HRESIMS analyses, and the absolute configurations were further confirmed by comparison of calculated and experimental electronic circular dichroism (ECD) curves. The cytotoxicity of isolates was evaluated on five human tumor cell lines, <strong>1</strong> and <strong>3</strong> showed moderate cytotoxic activities against HL-60.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"220 ","pages":"Article 109629"},"PeriodicalIF":2.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115649","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}
Pub Date : 2025-05-14DOI: 10.1016/j.steroids.2025.109630
Nguyen Manh Ha , Ninh The Son
Background
Sarcococca species (the family Buxaceae), containing a large number of steroidal alkaloids, were often used as medicinal plants for treating various ailments, such as fever, pain, and inflammation.
Objective
The current study aims to highlight the natural observation and pharmacological actions of Sarcococca steroidal alkaloids and related compounds.
Methods
Scientific literature of phytochemical studies and pharmacological examinations of Sarcococca species were collected from four main sources: Google Scholar, Web of Science, PubMed, and journal websites. “Sarcococca” and “steroidal alkaloids” were the primary keywords to search for references. The study covers almost all English publications from the 1960 s to the present. ChemDraw Ultra 12.0 was used to draw chemical structures of phytochemicals.
Results
Phytochemical results indicated that about 170 secondary metabolites have been detected in Sarcococca, of which 144 compounds (84.7%) can be classified as steroidal alkaloids. Other classes included sterols, triterpenoids, flavonoids, and mono-phenols. Sarcococca crude plant extracts, fractions, and their steroidal alkaloid isolates have pharmacological properties, such as cytotoxic, antimicrobial, antioxidative, antiinflammatory, antileishmanial, antiplasmodial, and antidiabetic activities. They were also recorded to protect against harmful conditions to the neurons, liver, and gastrointestinal system, and exert vasorelaxant, analgesic, estrogen biosynthesis, and nematicidal activities. Some steroidal alkaloids are better than the standard drugs to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Generally, substituted groups at nitrogenous atoms might be attributed to the differences in pharmacological results.
Conclusion
Advances in chromatographic isolations of steroidal alkaloids to obtain huge amounts are necessary. In vivo biological experiences and clinical testing are encouraged.
豆蔻属植物（豆蔻科）含有大量的甾体生物碱，常被用作药用植物，用于治疗各种疾病，如发烧、疼痛和炎症。目的对麻豆甾体生物碱及其相关化合物的天然观察和药理作用进行综述。方法从谷歌Scholar、Web of Science、PubMed和期刊网站4个主要来源收集麻豆属植物化学研究和药理研究的科学文献。“可可”和“甾体生物碱”是检索文献的主要关键词。这项研究涵盖了从20世纪60年代到现在几乎所有的英语出版物。使用ChemDraw Ultra 12.0绘制植物化学物质的化学结构。结果经植物化学鉴定，豆蔻中检出约170种次生代谢物，其中144种（84.7%）可归为甾体类生物碱。其他种类包括甾醇、三萜、类黄酮和单酚类。麻科植物粗提取物、馏分及其分离的甾体生物碱具有药理特性，如细胞毒性、抗菌、抗氧化、抗炎、抗利什曼原虫、抗疟原虫和抗糖尿病活性。它们还被记录为防止对神经元、肝脏和胃肠道系统的有害条件，并发挥血管松弛剂、镇痛剂、雌激素生物合成和杀线虫活性。部分甾体生物碱对乙酰胆碱酯酶（AChE）和丁基胆碱酯酶（BChE）的抑制作用优于标准药物。一般来说，氮原子上的取代基可归因于药理学结果的差异。结论为了获得大量的甾体生物碱，有必要在色谱分离方面取得进展。鼓励进行体内生物学实验和临床试验。
{"title":"Sarcococca species: A source of bioactive steroidal alkaloids – A review","authors":"Nguyen Manh Ha , Ninh The Son","doi":"10.1016/j.steroids.2025.109630","DOIUrl":"10.1016/j.steroids.2025.109630","url":null,"abstract":"<div><h3>Background</h3><div><em>Sarcococca</em> species (the family Buxaceae), containing a large number of steroidal alkaloids, were often used as medicinal plants for treating various ailments, such as fever, pain, and inflammation.</div></div><div><h3>Objective</h3><div>The current study aims to highlight the natural observation and pharmacological actions of <em>Sarcococca</em> steroidal alkaloids and related compounds.</div></div><div><h3>Methods</h3><div>Scientific literature of phytochemical studies and pharmacological examinations of <em>Sarcococca</em> species were collected from four main sources: Google Scholar, Web of Science, PubMed, and journal websites. “<em>Sarcococca</em>” and “steroidal alkaloids” were the primary keywords to search for references. The study covers almost all English publications from the 1960 s to the present. ChemDraw Ultra 12.0 was used to draw chemical structures of phytochemicals.</div></div><div><h3>Results</h3><div>Phytochemical results indicated that about 170 secondary metabolites have been detected in <em>Sarcococca</em>, of which 144 compounds (84.7%) can be classified as steroidal alkaloids. Other classes included sterols, triterpenoids, flavonoids, and <em>mono</em>-phenols. <em>Sarcococca</em> crude plant extracts, fractions, and their steroidal alkaloid isolates have pharmacological properties, such as cytotoxic, antimicrobial, antioxidative, antiinflammatory, antileishmanial, antiplasmodial, and antidiabetic activities. They were also recorded to protect against harmful conditions to the neurons, liver, and gastrointestinal system, and exert vasorelaxant, analgesic, estrogen biosynthesis, and nematicidal activities. Some steroidal alkaloids are better than the standard drugs to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Generally, substituted groups at nitrogenous atoms might be attributed to the differences in pharmacological results.</div></div><div><h3>Conclusion</h3><div>Advances in chromatographic isolations of steroidal alkaloids to obtain huge amounts are necessary. <em>In vivo</em> biological experiences and clinical testing are encouraged.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"220 ","pages":"Article 109630"},"PeriodicalIF":2.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071821","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}
Pub Date : 2025-05-09DOI: 10.1016/j.steroids.2025.109628
Muhammad Hammad Mustafa , Fayyaz-ur Rehman , Muhammad Ali , Mohsin Javed , Nazir Ahmad , Tayyaba Shafique , Ammar Zidan , Ali Bahadur , Shahid Iqbal , Sajid Mahmood , Abd-ElAziem Farouk , Ibrahim Jafri
Newcastle disease virus (NDV) classified in the Avian avulavirus 1 [genus Orthoavulavirus, subfamily Avulavirinae, family Paramyxoviridae] constitutes a serious financial risk to the global poultry market. Available vaccines do not show good results in catering to the virus. Currently there is no FDA-approved drug to treat the disease. Nucleoprotein (NP) is a structural protein playing that constitutes a serious financial risk to the global poultry market.a valuable role in the virus replication process and encapsidation. This study is an effort to screen phytochemicals, from the plant family Moringaceae, as potential inhibitors of the N protein. ADMET (adsorption, distribution, metabolism, excretion and toxicity) analysis was performed to screen potential phytochemicals with drug likeliness. Molecular Docking was performed for the binding affinities. Gas Chromatography-Mass Spectrometry (GC–MS) and Density Function Theory (DFT) were performed to evaluate the phytochemicals bioavailability and reactivity, respectively. The stability of protein–ligand complexes was examined by 50 ns MD simulations and MM/PBSA values were calculated. Out of 128 phytochemicals, 22 phytochemicals were selected following ADMET screening. Based on the binding energies and the number of H bonding the following 10 phytochemicals were suggested as potential inhibitors to N protein of NDV – cis-11,14-eicosadienoic acid methyl ester, aurantiamide acetate, α-tocopherol, 4,8,12,16-tetramethylheptadecan-4-olide, 3,7,11,15-tetramethyl-2-hexadecen-1-ol, β-amyrin, β-sitosterol-3-O-β-d-galactopyranoside, α-amyrin, pterygospermin and sitogluside. Furthermore, DFT results showed that the 4 pytochemicals – Cis-11,14-eicosadienoic acid methyl ester, aurantiamide acetate, α-tocopherol, and 3,7,11,15-tetramethyl-2-hexadecen-1-ol were most reactive and thus could be used as potential inhibitors of NDV N protein. Further studies are required to validate the selected four phytochemicals as drug candidates against NDV.
新城疫病毒（NDV）属禽阿武拉病毒1[原阿武拉病毒属，阿武拉病毒亚科，副粘病毒科]，对全球家禽市场构成严重的金融风险。现有疫苗在适应病毒方面没有显示出良好的效果。目前还没有fda批准的治疗这种疾病的药物。核蛋白（NP）是一种结构蛋白，对全球家禽市场构成严重的金融风险。在病毒复制过程和封装过程中发挥重要作用。本研究旨在筛选辣木科植物中可能抑制N蛋白的化学物质。ADMET（吸附、分布、代谢、排泄和毒性）分析筛选具有药物可能性的潜在植物化学物质。结合亲和度进行分子对接。采用气相色谱-质谱（GC-MS）和密度泛函理论（DFT）分别评价植物化学物质的生物利用度和反应性。通过50 ns MD模拟检测了蛋白质-配体复合物的稳定性，并计算了MM/PBSA值。在128种植物化学物质中，通过ADMET筛选选择了22种植物化学物质。根据结合能和H键的数目，提出了以下10种植物化学物质作为新冠病毒N蛋白的潜在抑制剂：顺式-11,14-二十碳二烯酸甲酯、醋酸金酰胺、α-生育酚、4,8,12,16-四甲基十七烷-4-内酯、3,7,11,15-四甲基-2-十六烯-1-醇、β-amyrin、β-谷甾醇-3- o -β-d-半乳糖苷、α-amyrin、pterygospermin和sitogluside。此外，DFT结果表明，顺式-11,14-二十二烯酸甲酯、醋酸金酰胺、α-生育酚和3,7,11,15-四甲基-2-十六烯-1-醇4种化学物质的活性最强，可以作为NDV N蛋白的潜在抑制剂。需要进一步的研究来验证所选的四种植物化学物质作为抗NDV的候选药物。
{"title":"In silico analysis of Moringaceae derived potential drug-like compounds against Newcastle disease virus","authors":"Muhammad Hammad Mustafa , Fayyaz-ur Rehman , Muhammad Ali , Mohsin Javed , Nazir Ahmad , Tayyaba Shafique , Ammar Zidan , Ali Bahadur , Shahid Iqbal , Sajid Mahmood , Abd-ElAziem Farouk , Ibrahim Jafri","doi":"10.1016/j.steroids.2025.109628","DOIUrl":"10.1016/j.steroids.2025.109628","url":null,"abstract":"<div><div>Newcastle disease virus (NDV) classified in the <em>Avian avulavirus 1</em> [genus <em>Orthoavulavirus</em>, subfamily <em>Avulavirinae</em>, family <em>Paramyxoviridae</em>] constitutes a serious financial risk to the global poultry market. Available vaccines do not show good results in catering to the virus. Currently there is no FDA-approved drug to treat the disease. Nucleoprotein (NP) is a structural protein playing that constitutes a serious financial risk to the global poultry market.a valuable role in the virus replication process and encapsidation. This study is an effort to screen phytochemicals, from the plant family Moringaceae, as potential inhibitors of the N protein. ADMET (adsorption, distribution, metabolism, excretion and toxicity) analysis was performed to screen potential phytochemicals with drug likeliness. Molecular Docking was performed for the binding affinities. Gas Chromatography-Mass Spectrometry (GC–MS) and Density Function Theory (DFT) were performed to evaluate the phytochemicals bioavailability and reactivity, respectively. The stability of protein–ligand complexes was examined by 50 ns MD simulations and MM/PBSA values were calculated. Out of 128 phytochemicals, 22 phytochemicals were selected following ADMET screening. Based on the binding energies and the number of H bonding the following 10 phytochemicals were suggested as potential inhibitors to N protein of NDV – <em>cis</em>-11,14-eicosadienoic acid methyl ester, aurantiamide acetate, α-tocopherol, 4,8,12,16-tetramethylheptadecan-4-olide, 3,7,11,15-tetramethyl-2-hexadecen-1-ol, β-amyrin, β-sitosterol-3-O-β-<span>d</span>-galactopyranoside, α-amyrin, pterygospermin and sitogluside. Furthermore, DFT results showed that the 4 pytochemicals – <em>Cis</em>-11,14-eicosadienoic acid methyl ester, aurantiamide acetate, α-tocopherol, and 3,7,11,15-tetramethyl-2-hexadecen-1-ol were most reactive and thus could be used as potential inhibitors of NDV N protein. Further studies are required to validate the selected four phytochemicals as drug candidates against NDV.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"219 ","pages":"Article 109628"},"PeriodicalIF":2.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935691","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}
Pub Date : 2025-05-06DOI: 10.1016/j.steroids.2025.109627
Peter Langer
Palladium catalyzed cross-coupling reactions of estrone allow for the synthesis of a variety of substituted steroids which are not readily available by other methods. Products include various alkynylated and arylated estrones and 13α-estrones, 16-arylmethylidene-3-O-methylestrones and 16-alkynylmethylidene-3-O-methylestrones. Reactions usually proceed with excellent chemo- and regioselectivity and exhibit a broad functional group tolerance. In several cases, the estrone derivatives prepared proved to be active and selective inhibitors of alkaline phosphatases or exhibited considerable antiproliferative activities.
钯催化雌酮的交叉偶联反应允许合成各种替代类固醇，这是不易通过其他方法获得的。产品包括各种炔基化和芳基化雌酮和13α-雌酮，16-芳基甲基-3- o -甲基甾酮和16-炔基甲基-3- o -甲基甾酮。反应通常以优异的化学选择性和区域选择性进行，并表现出广泛的官能团耐受性。在一些情况下，所制备的雌酮衍生物被证明是活性和选择性的碱性磷酸酶抑制剂或表现出相当大的抗增殖活性。
{"title":"Palladium-catalyzed cross-coupling reactions of estrone","authors":"Peter Langer","doi":"10.1016/j.steroids.2025.109627","DOIUrl":"10.1016/j.steroids.2025.109627","url":null,"abstract":"<div><div>Palladium catalyzed cross-coupling reactions of estrone allow for the synthesis of a variety of substituted steroids which are not readily available by other methods. Products include various alkynylated and arylated estrones and 13α-estrones, 16-arylmethylidene-3-<em>O</em>-methylestrones and 16-alkynylmethylidene-3-<em>O</em>-methylestrones. Reactions usually proceed with excellent chemo- and regioselectivity and exhibit a broad functional group tolerance. In several cases, the estrone derivatives prepared proved to be active and selective inhibitors of alkaline phosphatases or exhibited considerable antiproliferative activities.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"219 ","pages":"Article 109627"},"PeriodicalIF":2.1,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916438","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}
Pub Date : 2025-05-01DOI: 10.1016/j.steroids.2025.109626
Karina Sequeira , Soledad Henríquez , Paulina Kohen , Ariel Fuentes , Alejandro Tapia-Pizarro , Pablo Céspedes , Ana Godoy , Luigi Devoto
Purpose
The reduced circulating levels of dehydroepiandrosterone sulphate (DHEA-S) are associated with women with poor ovarian response, > 35 years old and low ovarian reserve (POSEIDON group 4, PG4) in cycles of controlled ovarian hyperstimulation. In the ovary, the uptake of DHEA-S is facilitated by the transmembrane organic anion-transporting polypeptide, OATP2B1, whereas in the cytoplasm, the hydrolysis of the inactive precursor DHEA-S into the biologically active steroid DHEA is catalyzed by the steroid sulfatase enzyme (STS). The objective of the present study was to evaluate DHEA and DHEA-S in serum and follicular fluid as well as the expression levels for STS and OATP2B1 in granulosa cells from women in PG4 compared to a control group (control) of age matched women with normal ovarian reserve and response to controlled ovarian hyperstimulation.
Methods
Prospective study which included 23 women who underwent in vitro fertilization. We compared women in PG4 (n = 13) with a control (n = 8). Transcript levels and the cellular distribution of STS and OATP2B1 transporter were determined by qPCR and immunofluorescence respectively in granulosa cells collected at the time of oocyte pick-up. Gene expression was analyzed according to age, circulating AMH, antral follicle count (AFC) along with DHEA-S and DHEA in serum and follicular fluid.
Results
Serum and follicular fluid analysis showed that DHEA-S was significantly decreased in PG4 compared to control, whereas no differences in DHEA concentrations were observed. Women in PG4 had significantly higher expression of STS and OATP2B1 mRNA (n = 13, p < 0.05) compared with those of the control.
Conclusion
Our results suggest that up-regulation of STS and OATP2B1 in granulosa cells from women in PG4 could be a compensatory mechanism to overcome the decreased circulating levels of DHEA-S possibly required as substrate for intraovarian production of DHEA.
{"title":"Steroid sulfatase and the transporter of sulfated steroids are upregulated in granulose cells from women of POSEIDON group 4 in controlled ovarian hyperstimulation for in vitro fertilization cycles","authors":"Karina Sequeira , Soledad Henríquez , Paulina Kohen , Ariel Fuentes , Alejandro Tapia-Pizarro , Pablo Céspedes , Ana Godoy , Luigi Devoto","doi":"10.1016/j.steroids.2025.109626","DOIUrl":"10.1016/j.steroids.2025.109626","url":null,"abstract":"<div><h3>Purpose</h3><div>The reduced circulating levels of dehydroepiandrosterone sulphate (DHEA-S) are associated with women with poor ovarian response, > 35 years old and low ovarian reserve (POSEIDON group 4, PG4) in cycles of controlled ovarian hyperstimulation. In the ovary, the uptake of DHEA-S is facilitated by the transmembrane organic anion-transporting polypeptide, OATP2B1, whereas in the cytoplasm, the hydrolysis of the inactive precursor DHEA-S into the biologically active steroid DHEA is catalyzed by the steroid sulfatase enzyme (STS). The objective of the present study was to evaluate DHEA and DHEA-S in serum and follicular fluid as well as the expression levels for STS and OATP2B1 in granulosa cells from women in PG4 compared to a control group (control) of age matched women with normal ovarian reserve and response to controlled ovarian hyperstimulation.</div></div><div><h3>Methods</h3><div>Prospective study which included 23 women who underwent in vitro fertilization. We compared women in PG4 (n = 13) with a control (n = 8). Transcript levels and the cellular distribution of STS and OATP2B1 transporter were determined by qPCR and immunofluorescence respectively in granulosa cells collected at the time of oocyte pick-up. Gene expression was analyzed according to age, circulating AMH, antral follicle count (AFC) along with DHEA-S and DHEA in serum and follicular fluid.</div></div><div><h3>Results</h3><div>Serum and follicular fluid analysis showed that DHEA-S was significantly decreased in PG4 compared to control, whereas no differences in DHEA concentrations were observed. Women in PG4 had significantly higher expression of STS and OATP2B1 mRNA (n = 13, p < 0.05) compared with those of the control.</div></div><div><h3>Conclusion</h3><div>Our results suggest that up-regulation of STS and OATP2B1 in granulosa cells from women in PG4 could be a compensatory mechanism to overcome the decreased circulating levels of DHEA-S possibly required as substrate for intraovarian production of DHEA.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"219 ","pages":"Article 109626"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912795","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}
Pub Date : 2025-04-30DOI: 10.1016/j.steroids.2025.109625
Weronika Broszkiewicz, Jakub Beda, Kamila Domińska
Limiting serum concentration in culture medium constitutes an environmental stress that disrupts cellular homeostasis and activates adaptive metabolism. This study aims to examine the impact of dexamethasone (DEX) on biological properties (e.g. viability, adhesion, migration) and glucose and lipid metabolism of prostate epithelial cells under stress conditions. The study used a non-tumorigenic human prostate cell line, PNT1A. In mild serum deprivation conditions, DEX, commonly used in the treatment of castration-resistant prostate cancer, also arrests normal prostate cells in the G0/G1 phase. Observed reduction in metabolic activity and limiting apoptosis of PNT1A cells as related to decreased expression of the NF-κB family and FOXO3 genes. Moreover, DEX modulated PNT1A migration by regulating cell plasticity thought capacity of adhesion to ECM proteins such as fibronectin and collagen I and IV. This was associated with changes in mRNA levels for the genes VIM, ZEB1 and ZEB2. Finally, it seems that dexamethasone helps PNT1A cells adapt to stress and enhance antioxidant defense, possibly by reprogramming lipid metabolism (e.g., LDLR, CPT1, MGLL), but not necessarily glucose metabolism.
{"title":"Effect of dexamethasone on biological properties and metabolic adaptations of normal prostate epithelial cells under mild serum conditions","authors":"Weronika Broszkiewicz, Jakub Beda, Kamila Domińska","doi":"10.1016/j.steroids.2025.109625","DOIUrl":"10.1016/j.steroids.2025.109625","url":null,"abstract":"<div><div>Limiting serum concentration in culture medium constitutes an environmental stress that disrupts cellular homeostasis and activates adaptive metabolism. This study aims to examine the impact of dexamethasone (DEX) on biological properties (e.g. viability, adhesion, migration) and glucose and lipid metabolism of prostate epithelial cells under stress conditions. The study used a non-tumorigenic human prostate cell line, PNT1A. In mild serum deprivation conditions, DEX, commonly used in the treatment of castration-resistant prostate cancer, also arrests normal prostate cells in the G0/G1 phase. Observed reduction in metabolic activity and limiting apoptosis of PNT1A cells as related to decreased expression of the NF-κB family and <em>FOXO3</em> genes. Moreover, DEX modulated PNT1A migration by regulating cell plasticity thought capacity of adhesion to ECM proteins such as fibronectin and collagen I and IV. This was associated with changes in mRNA levels for the genes <em>VIM</em>, <em>ZEB1</em> and <em>ZEB2</em>. Finally, it seems that dexamethasone helps PNT1A cells adapt to stress and enhance antioxidant defense, possibly by reprogramming lipid metabolism (e.g., <em>LDLR</em>, <em>CPT1</em>, <em>MGLL</em>), but not necessarily glucose metabolism.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"219 ","pages":"Article 109625"},"PeriodicalIF":2.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912798","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}
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