Steroids最新文献

{"title":"The effects of tamoxifen and its metabolites on circulating estrogen metabolites among pre- and postmenopausal women","authors":"Rajrupa Ghosh ,&nbsp;Ruth M. Pfeiffer ,&nbsp;Cody Ramin ,&nbsp;Xia Xu ,&nbsp;Paul C. Turner ,&nbsp;Xin He ,&nbsp;Rebecca Troisi ,&nbsp;Shaoqi Fan ,&nbsp;Gretchen L. Gierach ,&nbsp;Cher M. Dallal","doi":"10.1016/j.steroids.2025.109736","DOIUrl":"10.1016/j.steroids.2025.109736","url":null,"abstract":"<div><h3>Purpose</h3><div>Circulating estrogen metabolites of the 2-, 4- or 16-hydroxyestrone (OH) pathways may be differentially associated with breast cancer risk due to varying estrogenic and genotoxic activity. However, little is known about the influence of tamoxifen, an effective endocrine therapy, or its metabolites on estrogen metabolism.</div></div><div><h3>Methods</h3><div>Among women referred to tamoxifen therapy, 15 circulating estrogens and estrogen metabolites (EMs) were measured at baseline (pre-tamoxifen) and 12 months post-tamoxifen initiation using liquid chromatography-tandem mass spectrometry. Changes in EMs were assessed among women postmenopausal at baseline (n = 23) using paired t-tests. Using linear regression, cross-sectional associations between circulating tamoxifen, its three metabolites, and EMs were assessed 12-months post-tamoxifen among pre- (n = 33) and postmenopausal women (n = 27; includes four women who transitioned to postmenopausal during follow-up).</div></div><div><h3>Results</h3><div>Twelve months post-tamoxifen initiation, mean total EM concentrations decreased by 13.8% among postmenopausal women, primarily driven by decreases in 2-OH (15.3%) and 16-OH (17.2%) metabolites (p &lt; 0.05). Among women premenopausal at 12-month follow-up, circulating tamoxifen was positively associated with estrone (β = 1.24), estradiol (β =1.39), 2-OH metabolites (2-OHE1: β = 0.72, 2-ME1: β = 1.15), and all 16-OH metabolites (p &lt; 0.05). The tamoxifen metabolite, endoxifen, was positively associated with estrone (β = 10.1) and estradiol (β = 12.4), and select 2-OH and 16-OH metabolites (p &lt; 0.05). Positive associations were also observed between 4-hydroxy-tamoxifen and estrone, 2-OHE1, 2-ME1, 4-ME1, and E3 (p&lt;0.05). Among postmenopausal women, only <em>N</em>-desmethyltamoxifen was significantly associated with 3ME1 (β = 0.18, p = 0.02).</div></div><div><h3>Conclusion</h3><div>Tamoxifen and its metabolites were associated with changes in circulating EMs. Further research is needed to understand tamoxifen-induced EM changes in breast cancer prevention and management.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"226 ","pages":"Article 109736"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744612","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":"The impact of reproductive steroids on autosomal dominant polycystic kidney disease progression in women","authors":"Noor Saeed Hasan,&nbsp;Warren Thomas","doi":"10.1016/j.steroids.2025.109726","DOIUrl":"10.1016/j.steroids.2025.109726","url":null,"abstract":"<div><div>Autosomal dominant polycystic kidney disease (ADPKD) is a disease characterized by the growth of fluid filled cysts in the kidney. ADPKD arises due to a heritable mutation in the polycystic kidney disease 1 gene (PKD1) and polycystic kidney disease 2 gene (PKD2) ultimately leading to kidney failure. Incidence in males and females is equivalent, but differences arise in progression. This review brings together various studies regarding the impact of cyclic hormone changes on ADPKD progression, bringing attention to gaps in knowledge that needs to be addressed. Circulating hormones play a crucial role in the pathogenesis of the disease, particularly the renin angiotensin system. The physiological actions of estrogen tend to have a protective effect on the kidney, contributing to a slowed progression in females. The hormonal changes of the menstrual cycle and at menopause result in changes in pathology via blood pressure fluctuation, promotion of renal repair and prevention of renal scarring and damage. Signaling pathways that are involved in cyst growth such as cAMP, mTOR, MAPK/ERK, and PI3K/Akt are modulated by estrogen, providing insights into potential mechanisms. Estrogen-based hormonal therapy is being investigated for its efficacy in improving renal function post menopause.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"226 ","pages":"Article 109726"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701625","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":"Endoplasmic reticulum stress and steroidogenic dysfunction in Leydig cells: Molecular mechanisms of UPR-mediated testosterone regulation","authors":"Luc J. Martin","doi":"10.1016/j.steroids.2025.109735","DOIUrl":"10.1016/j.steroids.2025.109735","url":null,"abstract":"<div><div>This review aims to synthesize current evidence on how endoplasmic reticulum (ER) stress affects steroidogenic function in Leydig cells. It explores the mechanisms by which ER stress activates the unfolded protein response (UPR) and autophagy pathways, ultimately influencing testosterone production and cellular homeostasis. The central research question addresses how ER stress–induced signaling modulates the transcriptional regulation of key steroidogenic enzymes and contributes to age-related declines in androgen synthesis. A comprehensive literature review was conducted using recent findings from molecular, cellular, and animal studies focusing on ER stress signaling in Leydig cells. Studies examining the roles of UPR branches (PERK, IRE1, and ATF6), autophagy pathways, and pharmacological or natural compounds modulating ER stress were analyzed to identify the regulatory mechanisms being involved and potential therapeutic implications. Evidence indicates that unresolved ER stress impairs testosterone biosynthesis by suppressing the expression of genes related to steroidogenesis. Specifically, activations of XBP1, ATF4 and ATF6, as well as their nuclear translocations, may lead to the transcriptional repression of these genes. Conversely, pharmacological ER stress inhibitors and natural antioxidants may restore these protein levels, enhance testosterone production, and improve Leydig cell function. A thorough understanding of the UPR and autophagy in Leydig cells is critical for addressing male reproductive health. ER stress is established as a key factor in the pathophysiology of impaired steroidogenesis. Therefore, targeting these stress response pathways presents a promising strategy for developing novel therapeutic interventions for testosterone deficiency and associated reproductive disorders.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"226 ","pages":"Article 109735"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145726293","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":"Novel heterosteroids induce anabolic effects in human skeletal muscle cells: An integrated analysis of anabolic and catabolic signaling pathways","authors":"Linda Fabiola Pérez-Pérez ,&nbsp;Gabriel Guerrero-Luna ,&nbsp;Adrián Mendoza-Montalvo ,&nbsp;Nadia Olazo-Márquez ,&nbsp;Miguel López-Bartolo ,&nbsp;Pedro Pablo González-Pérez ,&nbsp;Jorge R. Juárez ,&nbsp;Sylvain Bernès ,&nbsp;Maura Cárdenas-García ,&nbsp;María Guadalupe Hernández-Linares","doi":"10.1016/j.steroids.2025.109737","DOIUrl":"10.1016/j.steroids.2025.109737","url":null,"abstract":"<div><div>The aim of this study was to investigate the anabolic potential of novel heterosteroids in human skeletal muscle cells. A library of new heterosteroids was synthesized by selectively modifying the A and B rings of steroidal sapogenins (diosgenin, sarsasapogenin, and hecogenin), with six library members (<strong>S1</strong>, <strong>D3</strong>, <strong>D5</strong>, <strong>D7</strong>, <strong>D8</strong> and <strong>D13</strong>) subsequently tested <em>in vitro</em>. Compound selection was based on computational modeling intracellular signaling pathways regulating muscle hypertrophy and atrophy, coupled with pharmacological potential evaluation using cheminformatics tools.</div><div>The anabolic activity of these compounds was evaluated in the ATCC PCS-950–010 HSkM cell line, which represents normal human skeletal muscle cells. Among the compounds tested, <strong>D5</strong> and <strong>D7</strong> increased protein synthesis by approximately 22 % and 14 %, respectively. Compound <strong>D8</strong> exhibited the most pronounced effect, increasing cell proliferation by approximately 50 %. Molecular docking and microarray analyses confirmed that <strong>D8</strong> stimulates anabolism through AKT, ERK and MAPK activation, revealing the complex interplay between MAPK, PI3K and GPCR signaling pathways in the regulation of muscle cell proliferation. These findings suggest that compounds <strong>D8</strong>, <strong>D5</strong>, and <strong>D7</strong> warrant further investigation in the context of muscle anabolism as potential therapeutic agents for targeting muscle atrophy.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"226 ","pages":"Article 109737"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145763985","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 unexpected oxidative E/F ring opening in the side chain of steroid sapogenins produced by silica gel supported Jones Reagent","authors":"Juan E. Hernández-Martínez,&nbsp;Karen M. Ruíz-Pérez,&nbsp;Jacqueline Sanchez-Flores,&nbsp;Martin A. Iglesias-Arteaga","doi":"10.1016/j.steroids.2025.109725","DOIUrl":"10.1016/j.steroids.2025.109725","url":null,"abstract":"<div><div>In contrast with previous results in which the spiroketal side chain of steroid sapogenin has proven to be unreactive to Jones Reagent, treatment these sapogenins with silica gel-supported Jones Reagent triggered the oxidative opening of the spirostanic side chain producing moderate to good yields of sapogenoic acids that bear carbonyl functions at C-16 and C-22 and a C-26 carboxylic group. Based on these findings, a procedure that allows the synthesis of sapogenoic acids minimizing contamination by chromium salts was designed.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"226 ","pages":"Article 109725"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145640036","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":"In vitro metabolic profiling of 6-chloro-testosterone and 6-ene-testosterone by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-time of flight (GC-TOF) mass spectrometry","authors":"Dayamin Martínez_Brito ,&nbsp;Carlotta Stacchini ,&nbsp;Cristiana Colamonici ,&nbsp;Davide Curcio ,&nbsp;Francesco Botrè ,&nbsp;Xavier de la Torre","doi":"10.1016/j.steroids.2025.109720","DOIUrl":"10.1016/j.steroids.2025.109720","url":null,"abstract":"<div><div>Among the phase-I reactions of 6-chloro-testosterone (6-CT), the reductive and oxidative dehalogenation, as well as the dehydrogenation, have been described here. One of the metabolic products could be the 6-ene-testosterone (6-ene-T). The goal of this work was to study the <em>in vitro</em> metabolism of 6-CT and 6-ene-T after incubation with human liver microsomes (HLM), analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-time-of-flight-mass spectrometry (GC-TOF).</div><div>6-CT showed a more extensive metabolism compared to 6-ene-T, with the formation of a larger number of metabolites. In contrast, 6-ene-T, which potentially preserves the C6<img>C7 double bond in most of its metabolites, showed fewer metabolites. Therefore, after incubation with HLM, the main metabolic routes of 6-ene-T are the oxidation of the hydroxyl group on C17β, retaining the double bond C6<img>C7 to form 6-ene-androstenedione, and the hydroxylation on C6. On the other hand 6-CT metabolism produced chlorinated and non-chlorinated metabolites as a result of the phase I reactions which included oxidation, reduction, hydroxylation and (oxidative and reductive) dehalogenation. Specifically for 6-CT, it should be considered that the introduction of a chlorine atom in the 6α position of T may lead to a shift in the metabolic pathway, favoring the formation of 5β-reduced metabolites over 5α-reduced metabolites, due to the steric and electronic effects of the chlorine atom on the interaction between the steroid molecule and the 5α-reductase enzyme.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109720"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565187","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":"The influence of the route of drug administration on the metabolic profile of trenbolone in doping control urine samples","authors":"Sophia Krombholz ,&nbsp;Thomas Piper ,&nbsp;Andreas Lagojda ,&nbsp;Dirk Kühne ,&nbsp;Mario Thevis","doi":"10.1016/j.steroids.2025.109716","DOIUrl":"10.1016/j.steroids.2025.109716","url":null,"abstract":"<div><div>Advances in analytical techniques have markedly improved the detection of anabolic–androgenic steroids (AAS) in doping controls. This represents a major success for anti-doping efforts, but at the same times raises concerns about inadvertent exposure – not limited to oral ingestion, but also via dermal contact or mucosal absorption. Evaluating the plausibility of such scenarios can be complex, not least because these routes of drug intake can also be deliberately used for doping purposes. Analytical data on transdermal or mucosal absorption and elimination of AAS can be valuable here, particularly regarding the metabolite pattern in urine samples that might help to assess the route of drug delivery. This study investigated the urinary excretion profile of trenbolone and its metabolites after oral, transdermal and buccal administration in healthy male volunteers. Urine samples collected over a period of one week following the administration of 10 <!--> <!-->mg of trenbolone were analyzed by LC-HRMS, with regard to potential differences in the metabolite profile across the different routes of drug intake. Major trenbolone metabolites were detectable in the urine samples of all participants, however the detection windows varied strongly: Buccal resorption resulted in faster elimination, whereas transdermal application resulted in prolonged detectability, compared to oral administration. A cysteine-conjugated metabolite (M15-cys) was identified that showed higher abundances following transdermal and buccal administration, suggesting its potential as a marker for non-oral intake. In light of the growing importance of transdermal uptake of doping agents, these results provide valuable data for interpreting doping control findings, potentially also relevant for structurally related AAS.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109716"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145507019","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":"LC-MS/MS quantitation of the primary reduced metabolites of progesterone in serum during the third trimester of human pregnancy reveals a potential role for 20β-hydroxyprogesterone and 5β-dihydroprogesterone in functional progesterone withdrawal","authors":"Edward Hinchliffe ,&nbsp;Alexander Heazell","doi":"10.1016/j.steroids.2025.109724","DOIUrl":"10.1016/j.steroids.2025.109724","url":null,"abstract":"<div><div>Progesterone (P4) is an essential steroid hormone synthesised by the placenta required for the maintenance of pregnancy. In humans, the metabolism of P4 has been implicated in functional P4 withdrawal prior to parturition. We have developed a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantitation in human serum of pregnenolone, P4 and its four primary reduced metabolites; 20α-hydroxyprogesterone (20α-OHP), 20β-hydroxyprogesterone (20β-OHP), 5α-dihydroprogesterone (5α-DHP) and 5β-dihydroprogesterone (5β-DHP). Following solid phase extraction, chromatographic baseline separation of each steroid was achieved using a biphenyl stationary phase within a 10.0 min runtime, followed by MS detection on a Sciex 6500+. The LC-MS/MS method was validated in accordance with published guidelines, confirming acceptable analytical performance pertaining to linearity, imprecision, accuracy, sensitivity, matrix effects, specificity and carryover. The method was applied to a large cohort of third trimester pregnancies with verified uncomplicated neonatal outcomes. Maternal circulating concentrations of P4, 20α-OHP, 20β-OHP, and 5α-DHP positively correlated with fetal gestational age. The ratio of P4:20β-OHP declined significantly throughout the third trimester, whilst the ratio of P4:5β-DHP increased at full term from 40 weeks’ gestation. These findings may indicate a substantive role for β-reduction of P4 in the mechanics of functional P4 withdrawal, either via depletion of the overall pool of bioactive P4 or competitive binding of these metabolites to the P4 receptor in maternal and fetal tissue. Additionally, detailed characterisation of the normal maternal steroidome will facilitate the study of dysregulated placental steroidogenesis, which has been implicated in the pathogenesis of the major obstetric syndromes causing poor pregnancy outcomes.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109724"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615351","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":"Exploring the relationship between endogenous steroids and nausea and vomiting in pregnancy: A longitudinal prospective study","authors":"Jana Benešová ,&nbsp;Martin Hill ,&nbsp;Daniela Dlouhá ,&nbsp;Kateřina Roberts ,&nbsp;Jana Ullmann ,&nbsp;Peter Koliba ,&nbsp;Marta Velíková ,&nbsp;Šárka Kaňková","doi":"10.1016/j.steroids.2025.109701","DOIUrl":"10.1016/j.steroids.2025.109701","url":null,"abstract":"<div><div>Nausea and vomiting in pregnancy (NVP) affect approximately 70 % of women worldwide. It is thought to have an adaptive function in the first trimester, when it protects the mother and the fetus against potential dangers from the diet. Proximate causes of NVP include hormonal changes during pregnancy. This longitudinal prospective study examined associations between various endogenous steroids and NVP. In the first and third trimester, pregnant women (N = 179) completed the Index of Nausea, Vomiting, and Retching questionnaire (92.1 % of women reported at least some symptoms of NVP in the first trimester and 37.4 % in the third trimester) and we analyzed their blood serum concentrations of 91 endogenous steroids. In the first trimester, NVP intensity was significantly positively associated with progesterone metabolites from the C21 5α/β-reduced steroid group (e.g., allopregnanolone sulfate) and with conjugated 5α-androstane-3α,17β-diol and conjugated 5α-androstane-3β,17β-diol. In the third trimester, we found significant negative associations between NVP and progesterone, conjugated testosterone, 7-oxo-DHEA, 5-androstene-3β,16α,17β-triol sulfate, some C21 Δ⁵ steroids (e.g., pregnenolone sulfate, 17-hydroxypregnenolone sulfate), and C21 5α/β-reduced steroids (such as allopregnanolone sulfate and conjugated pregnanolone). Our findings suggest that sulfated 3α-hydroxy-5α-steroids may contribute to NVP in early pregnancy by affecting brainstem regions involved in the vomiting reflex. In late pregnancy, higher levels of immunomodulatory androstanes and progesterone may reduce NVP severity via immune regulation and smooth muscle relaxation.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109701"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329918","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":"Microbial catalyzed derivatization of canrenone with Glomerella fusarioides, and Cunninghamella blakesleeana, and evaluation of aromatase inhibitory activity of the resulting metabolites","authors":"Ambreen Aziz ,&nbsp;Atia-tul-Wahab ,&nbsp;Ghulam Farooq ,&nbsp;Nimra Naveed Shaikh ,&nbsp;Sammer Yousuf ,&nbsp;Humaira Zafar ,&nbsp;Zaheer Ahmed ,&nbsp;M. Iqbal Choudhary","doi":"10.1016/j.steroids.2025.109704","DOIUrl":"10.1016/j.steroids.2025.109704","url":null,"abstract":"<div><div>The purpose of this study was to identify potential aromatase inhibitors, which might play a role in preventing breast cancer. The fungal-catalyzed microbial transformation of an anti-mineralocorticoid, canrenone (<strong>1</strong>), was catalyzed by <em>Glomerella fusarioides</em>, and <em>Cunninghamella blakesleeana</em>. Bioconversion of canrenone (<strong>1</strong>) with <em>G. fusarioides</em> provided a new polar metabolite <strong>2</strong>, and two known metabolites <strong>3</strong> and <strong>4</strong>, while <em>C. blakesleana</em> transformed compound <strong>1</strong> into two known polar metabolites <strong>4</strong>, and <strong>5</strong>. Modern spectroscopic techniques were employed to identify the structures of metabolites as 1-dehydro-11<em>α</em>-hydroxycanrenone (<strong>2</strong>), 1-dehydrocanrenone (<strong>3</strong>), 11<em>α</em>-hydroxycanrenone (<strong>4</strong>), and 11<em>β</em>-hydroxycanrenone (<strong>5</strong>). The SingleCrystal X-ray Diffraction (SCXRD) based structures of metabolites <strong>2</strong>, and <strong>3</strong> are reported here for the first time. Canrenone (<strong>1</strong>) and the resulting metabolites <strong>2</strong>–<strong>4</strong> were evaluated for their human aromatase inhibitory activity. Compounds <strong>1</strong>–<strong>4</strong> showed the IC₅₀ values of 0.288 ± 0.0392, 0.372 ± 0.002, 0.328 ± 0.0083, and 1.102 ± 0.099, µM comparable to the standard drug, exemestane (0.26 ± 0.011 µM). All transformed products were found non-cytotoxic to human fibroblast (BJ) cell line. Furthermore, the docking studies predicted the interaction of potential inhibitors with the active site residues of the enzyme <em>via</em> hydrogen bonding and other non-covalent interactions. Simulation studies predicted the formation of stable enzyme-inhibitor complexes with no or insignificant perturbation during the simulation time of 100 nsec. Hence, these inhibitors may serve as preliminary hits for drug discovery against ER+ breast cancer.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109704"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370468","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}