Steroids[JOURNAL]
Sun
200 papers
Steroidal alkaloids as multi-target therapeutics for the treatment of endometriosis.
Shirodkar S, Doshi G
Steroids · 2026 Jul · PMID 42401307 · Publisher ↗
Endometriosis is a chronic inflammatory disease characterised by ectopic endometrial tissue, progressive fibrosis and chronic pain, with a pathogenesis that goes beyond oestrogen dependence. The central question this rev...
Endometriosis is a chronic inflammatory disease characterised by ectopic endometrial tissue, progressive fibrosis and chronic pain, with a pathogenesis that goes beyond oestrogen dependence. The central question this review seeks to answer is: are steroidal alkaloids - nitrogenous plant-derived steroids with a unique structure - a mechanistically sensible, non-hormonal alternative that can simultaneously target the inflammatory, fibrotic and epigenetic drivers of endometriotic lesion persistence, while preserving fertility and avoiding systemic hormonal suppression? A growing body of evidence points to non-hormonal molecular networks including immune dysregulation, angiogenesis, and resistance to apoptosis as drivers of lesion persistence [1]. These molecular disturbances are associated with treatment resistance and limit the long-term efficacy of hormone-based therapies. This review synthesises recent mechanistic advances that describe the non-hormonal signalling pathways that maintain endometriotic lesions, with a specific emphasis on NF-κB-mediated sterile inflammation, inflammasome activation, PI3K/Akt/mTOR-dependent survival signalling, Hedgehog-driven fibrosis and epigenetic repression of progesterone receptor expression. Steroidal alkaloids are critically reviewed as multitarget modulators suppressing inflammatory signalling, inhibiting invasive and fibrotic remodelling, and restoring apoptotic sensitivity in this pathophysiological context, without direct systemic oestrogen deprivation. Structural determinants of steroidal alkaloid activity, including glycosylation status, nitrogen topology and configuration of the steroidal scaffold, are discussed in the context of pathway selectivity, pharmacokinetics and toxicity. Preclinical in vitro and in vivo evidence is critically reviewed in the context of key translational limitations such as bioavailability constraints, narrow therapeutic index and teratogenic risk from developmental pathway inhibition. This review highlights steroidal alkaloids as a mechanistically rational, non-hormonal approach to target lesion persistence and fibrosis in endometriosis, integrating molecular, pharmacological and structural insights, and outlines the major hurdles that must be overcome for clinical translation. The main objective of this review is to address a specific unanswered question: can steroidal alkaloids with their multitarget pharmacology offer a biologically coherent, non-hormonal strategy for the treatment of endometriosis that goes beyond oestrogen deprivation to target the molecular machinery of lesion survival, fibrosis and immune dysregulation. This question is addressed by reviewing the nonhormonal signalling networks that support ectopic lesions, the structural and pharmacokinetic properties of steroidal alkaloids that are relevant to these pathways, and the translational challenges that need to be addressed for clinical translation.
Emerging trends for therapeutic valuation of Cyclopamine: Structural features, mechanism of action, and formulation strategies.
Desai H, Eknure C, Kale A … +3 more , Pawar B, Gholap A, Bachhav Y
Steroids · 2026 Jul · PMID 42392345 · Publisher ↗
Cyclopamine, a jervatrum-type steroidal alkaloid from Veratrum species, is one of the earliest natural inhibitors of the Hedgehog (Hh) signaling pathway and was instrumental in identifying Smoothened (SMO) as a therapeut...
Cyclopamine, a jervatrum-type steroidal alkaloid from Veratrum species, is one of the earliest natural inhibitors of the Hedgehog (Hh) signaling pathway and was instrumental in identifying Smoothened (SMO) as a therapeutic target in oncology. Initially recognised as a potent teratogen, its activity was later attributed to direct SMO inhibition, suppressing GLI-mediated transcription and revealing Hh signaling as a driver of diverse malignancies, including basal cell carcinoma, medulloblastoma, pancreatic ductal adenocarcinoma, and glioblastoma. Despite strong pathway specificity, clinical translation of cyclopamine is hindered by poor solubility, acid lability, low bioavailability, and teratogenic risk. Medicinal chemistry optimization, prodrug strategies, and advanced nanocarrier systems, such as micelles, lipid nanoparticles, albumin carriers, and polymer-drug conjugates, have been explored to overcome these limitations and enable tumor-targeted delivery. Moreover, cyclopamine analogues have inspired the development of clinically approved SMO inhibitors, validating the pathway as a therapeutic target. Collectively, cyclopamine's trajectory from developmental toxicant to molecular probe and lead scaffold underscores its enduring impact on Hh-directed drug discovery and highlights the ongoing relevance of formulation-driven strategies in oncology.
The antiproliferative and antimigratory properties of the 3-biotin-B-norcholesteryl benzimidazole derivative in MCF-7 cells are mediated through G1 phase arrest and apoptosis.
Li Y, Gan B, Chen S … +6 more , Huang X, Liu Z, Zhu Z, Huang Y, Zhan J, Gan C
Steroids · 2026 Jul · PMID 42386053 · Publisher ↗
Our research group has previously constructed a series of 3-biotin-B-norcholesteryl benzimidazole derivatives; nevertheless, their underlying biological mechanisms against breast cancer remain poorly defined. In the pres...
Our research group has previously constructed a series of 3-biotin-B-norcholesteryl benzimidazole derivatives; nevertheless, their underlying biological mechanisms against breast cancer remain poorly defined. In the present work, three representative analogs were assessed in MCF-7 human breast cancer cells to explore whether the optimal lead candidate restrains tumor cell proliferation and migration via modulating apoptosis and cell-cycle progression. MTT and colony formation assays identified compound 1 as the most potent antiproliferative agent, with an IC of 6.53 μM in MCF-7 cells, which outperformed tamoxifen under identical experimental conditions. By contrast, compound 1 exhibited a markedly elevated IC of 15.19 μM in non-tumorigenic MCF10A human mammary epithelial cells, yielding a selectivity index of 2.33 toward MCF-7 cells. Furthermore, compound 1 suppressed colony formation and scratch wound closure in a concentration-dependent fashion. Morphological examination combined with Hoechst 33258 staining revealed hallmark apoptotic phenotypes, including cellular shrinkage, apoptotic body generation, as well as nuclear condensation and fragmentation. Annexin V-FITC/PI double-staining flow cytometry validated concentration-dependent apoptosis predominantly featured by early apoptotic populations, while PI cell cycle staining demonstrated prominent G1-phase cell cycle arrest. RT-qPCR quantification revealed that compound 1 treatment markedly upregulated the transcript levels of p53 and c-Myc yet downregulated MDM2, whereas the expression of ERα remained statistically unaltered. Collectively, these data demonstrate that compound 1 elicits antiproliferative and antimigratory activities in MCF-7 cells by triggering robust early apoptosis and G1-phase arrest, an effect mediated at least partially through regulation of the MDM2-p53 signaling axis. Taken together, these observations establish compound 1 as a promising antitumor lead scaffold for subsequent structural modification. Further investigations regarding its selectivity profile, systemic toxicity, pharmacokinetic properties, and in vivo therapeutic efficacy are therefore warranted.
Development and validation of an LC-MS method for quantification of sex steroid hormones in skeletal muscle.
Engman V, Lamon S, Mason S
Steroids · 2026 Jun · PMID 42341862 · Publisher ↗
Sex steroid hormones are not exclusively localised in the circulation and can be found in numerous extragonadal tissues, in concentrations unrelated to the circulating fraction. Existing methodology to measure intramuscu...
Sex steroid hormones are not exclusively localised in the circulation and can be found in numerous extragonadal tissues, in concentrations unrelated to the circulating fraction. Existing methodology to measure intramuscular steroid hormone concentrations includes both immune-based assays and liquid chromatography-mass spectrometry (LC-MS), the gold standard for hormone measurements. To date, no LC-MS based methods validation has been published on the measurement of intramuscular sex steroid hormones, despite clear biological relevance. Here, we describe the development and validation of a simple, high-throughput LC-MS Orbitrap method for the measurement of 10 intramuscular sex steroid hormones, namely pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, epitestosterone, dihydrotestosterone, oestrone, oestradiol, and oestriol. In brief, isotope labelled standards were added to 5-6 mg of lyophilised muscle tissue, homogenised and extracted with ethyl acetate. The extracts were dried down and sequentially derivatised with 1-methylimidazole-2-sulfonyl chloride and hydroxylamine hydrochloride to target both the phenolic hydroxy groups and oxo groups. The limit of detection was 1.0 ± 1.0 pg/mg (range 0.36-3.26 pg/mg), with a R > 0.99 for all analytes. Matrix effects were 90-110% for all analytes except for dihydrotestosterone (143.6%), and precision was <10 CV% for all analytes in the presence of a muscle matrix. Our method allows for 20-40 samples to be prepared in ∼4 h, with a sample data acquisition time of 13 min. Moreover, our method provides the opportunity for specific analysis of steroid hormone concentrations in skeletal muscle, allowing target tissue specificity instead of relying on proxy measures from the circulation.
Circulating 4β-hydroxycholesterol as a biomarker of CYP3A4 activity: beyond drug development.
Passarelli MN
Steroids · 2026 Jun · PMID 42251959 · Publisher ↗
Intestinal and hepatic expression of cytochrome P450 3A4 (CYP3A4) is essential to the oxidative metabolism of many steroids, environmental toxins, and pharmaceutical drugs. The enzyme also produces 4β-hydroxycholesterol...
Intestinal and hepatic expression of cytochrome P450 3A4 (CYP3A4) is essential to the oxidative metabolism of many steroids, environmental toxins, and pharmaceutical drugs. The enzyme also produces 4β-hydroxycholesterol (4β-OHC) from cholesterol, an oxysterol involved in several metabolic signaling pathways and detectable in human circulation. Circulating 4β-OHC is increasingly used in drug development research as an endogenous biomarker of CYP3A4 activity to understand agent metabolism and the potential for drug-drug interactions. The relatively long half-life of 4β-OHC in blood provides temporal stability, while still retaining sensitivity to increase 2- to 4-fold within a week in response to a strong CYP3A4 inducer. Beyond pharmacometric studies, circulating 4β-OHC is emerging as a biomarker of cumulative CYP3A4-related detoxification capacity in epidemiologic studies of liver disease, renal disease, hypertension, diabetes, cancer, and other conditions. Discoveries in lipid biology have distinguished 4β-OHC from other oxysterols, revealing mechanisms by which endobiotic and xenobiotic metabolism can disrupt the homeostasis of cholesterol, fatty acids, and glucose. This review summarizes the expanding relevance of circulating 4β-OHC in epidemiologic research, focusing on clinical and demographic characteristics as sources of variation. Consistent with between-person variability in CYP3A4 activity, circulating 4β-OHC is typically higher for women, lean individuals, and genetically-determined CYP3A5 expressers, factors potentially affecting its application in both drug optimization and disease phenotyping.
Impact of glycosylation position on flavonoid isomers' inhibition of breast cancer-associated enzyme CYP1B1.
Wang Y, Guo Q, Lu J … +2 more , Tian Y, Meng X
Steroids · 2026 Jun · PMID 42251958 · Publisher ↗
Isomerism in natural flavonoids critically influences enzyme inhibitory activity, particularly toward cytochrome P450 enzymes. Mangiferin and isomangiferin, two C-glycosyl flavonoid isomers differing only in glycosidic s...
Isomerism in natural flavonoids critically influences enzyme inhibitory activity, particularly toward cytochrome P450 enzymes. Mangiferin and isomangiferin, two C-glycosyl flavonoid isomers differing only in glycosidic substitution position on the xanthone skeleton, serve as ideal model compounds for probing structure-activity relationships against CYP1B1, a breast cancer-associated enzyme involved in carcinogen activation. However, whether such glycosidic positional isomerism affects CYP1B1 inhibition and binding behavior remains unknown. Here, the inhibitory effects and molecular mechanisms of mangiferin and isomangiferin toward CYP1B1 were systematically investigated using enzyme kinetics, quantum chemical calculations, molecular docking, and machine learning-based ADMET prediction. Kinetic analysis revealed that mangiferin inhibited CYP1B1 over 100-fold more potently than isomangiferin, exhibiting mixed-type inhibition, whereas isomangiferin showed non-competitive behavior. Quantum chemical calculations demonstrated that altered glycosidic positions shifted HOMO-LUMO energy distributions and electron density, affecting intermolecular interactions. Molecular docking identified key residues responsible for stronger mangiferin binding. ADMET prediction indicated favorable pharmacokinetics and low toxicity for both compounds. These results demonstrate that subtle changes in glycosidic substitution position can profoundly influence CYP1B1 inhibitory potency and binding mode of mangiferin and isomangiferin, providing mechanistic insight into structure-activity relationships of such isomers.
Synthesis NMR characterization and X-ray structure of α,β-unsaturated steroid spiroketal lactones. evaluation of cytotoxicity and anti-inflammatory activity.
Hernández-Martínez JE, Campos-Xolalpa N, Pérez-Gutiérez S … +2 more , Flores-Álamo M, Iglesias-Arteaga MA
Steroids · 2026 Jun · PMID 42250668 · Publisher ↗
Aldol condensation between different steroid sapogenins and pyruvic acid in the presence of BF·EtO, led to steroids with a α,β-unsaturated spiroketal lactone side chain that produced significant reduction on the producti...
Aldol condensation between different steroid sapogenins and pyruvic acid in the presence of BF·EtO, led to steroids with a α,β-unsaturated spiroketal lactone side chain that produced significant reduction on the production of nitric oxide in LPS-stimulated macrophages, suggesting potential anti-inflammatory activity. One of the obtained compounds showed strong cytotoxicity against HeLa cervical cancer cells.'
Physicochemical characterisation of difluprednate and 6α9α-difluoroprednisolone: Determination of solubility, pKa and LogP.
Baluci G, Buhagiar PI, Vella Szijj J … +2 more , Attard E, Sammut Bartolo N
Steroids · 2026 Jun · PMID 42248441 · Publisher ↗
Steroids are used in the treatment of diverse pathological conditions for their anti-inflammatory and immunosuppressive effects, with the mode of action being affected by their physicochemical characteristics. To date, d...
Steroids are used in the treatment of diverse pathological conditions for their anti-inflammatory and immunosuppressive effects, with the mode of action being affected by their physicochemical characteristics. To date, difluprednate (DFBA) has been characterised using computational methods which rely on the selected computational model and disregard external factors. The aim of the study was to determine the solubility, pKa and LogP of DFBA and its metabolite, 6α9α-difluoroprednisolone (DFP) using experimental methods. Methods using UV-Visible spectroscopy and High-Performance Liquid Chromatography (HPLC) were developed to determine the solubility and the pKa, LogD and LogP of the selected steroids. The steroids are soluble in acetonitrile and methanol, and are insoluble in water. DFBA achieved a solubility of 5.76 mg/mL and 0.81 mg/mL in acetonitrile and methanol, while DFP achieved solubility of 2.29 mg/mL and 0.16 mg/mL, respectively. DFBA had an average LogP value of 3.2, and DFP had an average LogP of 1.5. The pKa values for DFBA were 1.5 and 7.2 and for DFP, were 5.9 and 10.8. The characterisation of the physicochemical properties of DFBA and DFP can help support efficient formulation development.
Evaluation Of Dheas (Dehydroepiandrosterone Sulfate) Levels In Patients With Adrenal Adenomas Exhibiting Autonomous Cortisol Secretion.
Aksoydan Zubaroglu UP, Akkus G, Tetiker BT
Steroids · 2026 Jun · PMID 42242337 · Publisher ↗
BACKGROUND: Autonomous cortisol secretion (ACS) is the most common hormonal dysfunction in adrenal incidentalomas and is associated with increased cardiometabolic morbidity. Dehydroepiandrosterone sulfate (DHEAS), an ACT...
BACKGROUND: Autonomous cortisol secretion (ACS) is the most common hormonal dysfunction in adrenal incidentalomas and is associated with increased cardiometabolic morbidity. Dehydroepiandrosterone sulfate (DHEAS), an ACTH-dependent adrenal steroid, may decrease in ACS due to hypothalamic-pituitary-adrenal axis suppression. This study evaluated the diagnostic utility of DHEAS and DHEAS-based ratios, particularly within a dexamethasone suppression test (DST)-integrated framework, for differentiating ACS from non-functioning adrenal adenomas (NFA). METHODS: In this retrospective single-center study, records of 433 patients followed for adrenal incidentaloma between 2015 and 2021 were reviewed. After applying predefined criteria, 67 patients were included: 35 with ACS and 32 with NFA. ACS was defined using a post-1 mg DST cortisol threshold of ≥ 1.8 µg/dL and confirmed with a two-day low-dose DST. Clinical, metabolic, biochemical, hormonal, and radiological parameters were analyzed. ROC analyses and logistic regression were performed, and internal validation was conducted using bootstrapping with 1,000 iterations. RESULTS: Comorbidities were more frequent in ACS. ACTH, DHEAS, DHEAS/cortisol ratio, DHEAS/1-mg DST cortisol ratio, and TyG index differed significantly between groups. Post-1 mg DST cortisol showed the highest discriminatory performance (AUC = 0.967). Although DHEAS alone had limited diagnostic utility, the DHEAS/1-mg DST cortisol ratio showed good discrimination (AUC = 0.884, 95% CI: 0.802-0.966) and remained the only independent predictor of ACS (OR: 0.931, 95% CI: 0.895-0.968, p < 0.001). TyG showed moderate discrimination but was not an independent predictor. CONCLUSION: The DHEAS/1-mg DST cortisol ratio may serve as a useful adjunctive marker for ACS-NFA differentiation, especially in borderline or ambiguous cases, but requires prospective external validation.
Preventive effects of estrogen and progesterone against adiposity are promoted by testosterone in ovariectomized female rats.
Takahashi A, Arata M, Noguchi H … +10 more , Purevdorj T, Tamura K, Takeda A, Sugimoto T, Shinohara A, Aoki H, Kinouchi R, Yoshida K, Iwasa T, Yamamoto Y
Steroids · 2026 Jun · PMID 42242336 · Publisher ↗
Some synthetic progestins contained in hormonal drugs (e.g., oral contraceptives) are known to have androgenic activity; however, the roles of such androgenic activity in the regulation of nutrition and metabolism remain...
Some synthetic progestins contained in hormonal drugs (e.g., oral contraceptives) are known to have androgenic activity; however, the roles of such androgenic activity in the regulation of nutrition and metabolism remain unclear. Here, we examined the effects of testosterone on nutrition- and metabolism-related parameters in the presence of both estrogen and progesterone. Female rats were ovariectomized and randomly assigned to a no-treated group (OVX), an estrogen and progesterone-treated group (OVX+EP), or an estrogen, progesterone, and testosterone-treated group (OVX+EPT). Subsequently, change in body weight, food intake, fat weight, adipocyte size, and peripheral and central levels of feeding-related factors were evaluated. The results indicated that body weight and food intake were lower in OVX+EP and OVX+EPT than in OVX, whereas these parameters did not differ between OVX+EP and OVX+EPT. Although fat weight and/or adipocyte size did not differ between OVX+EP and OVX, these parameters were lower in OVX+EPT than in OVX and OVX+EP. Conversely, serum leptin and hypothalamic proopiomelanocortin mRNA levels, which are anorectic factors, were lower in OVX+EPT than in OVX+EP and OVX, suggesting that these are preventive reactions. These findings indicate that estrogen and progesterone supplementation in OVX rats exert some favorable effects on metabolic and nutritional conditions, and that the additional administration of testosterone may promote these actions. Thus, although the androgenic activity of progestin used in some hormonal drugs may not fully correspond to the effects of testosterone in the presence of estrogen and progesterone, testosterone does not necessarily exert adverse metabolic effects and may offer preventive effects against obesity and metabolic disordersunder these conditions.
Carnosic acid ameliorates methotrexate-induced male infertility: targeting testicular redox imbalance and nitric oxide/CGMP signaling.
Ajibare AJ, Adejumo MO, Akanbioluwa EF … +4 more , Adelokiki I, Akinfe O, Aransi-Ola KT, Akintoye OO
Steroids · 2026 Jun · PMID 42225222 · Publisher ↗
PURPOSE: Methotrexate (MTX), a folate antagonist used in the treatment of cancer and autoimmune disorders, unfortunately, induces testicular toxicity and impairs male fertility. Although the tissue-protective properties...
PURPOSE: Methotrexate (MTX), a folate antagonist used in the treatment of cancer and autoimmune disorders, unfortunately, induces testicular toxicity and impairs male fertility. Although the tissue-protective properties of Carnosic acid (CAR) are known, its effectiveness in mitigating MTX-induced reproductive toxicity has not been adequately studied. This study explores the protective role of CAR against the toxicity of MTX in rat testes. METHODS: Forty male Wistar rats were divided into four groups: control, MTX (20 mg/kg i.p., day 7), MTX + low-dose CAR (20 mg/kg p.o., 14 days), and MTX + high-dose CAR (40 mg/kg p.o., 14 days). On day 15, testicular tissue and serum were analyzed for oxidative stress markers (GSH, GPx, MDA), NO/cGMP pathway components (iNOS, NO, cGMP), inflammatory markers (NF- κB, IL-6), steroidogenesis parameters (total cholesterol, 3β-HSD, 17β-HSD), and hormonal levels (GnRH, FSH, LH, testosterone, estradiol). Histopathological examinations were conducted on testicular sections. RESULTS: MTX significantly reduced antioxidant levels, increased lipid peroxidation, disrupted NO/cGMP signaling, elevated inflammation, impaired steroidogenesis, and altered hormone levels, with evidence of histological changes. CAR, especially at higher doses, mitigated these effects, restoring antioxidant status, normalizing NO/cGMP signaling, reducing inflammation, enhancing steroidogenesis, and improving testicular morphology. CONCLUSION: CAR ameliorates MTX-induced adverse effects in the testes of rats via controlling redox balance, NO/cGMP signaling, inflammation, and steroidogenesis, with the potential of CAR to be used as a treatment to protect male reproductive function during therapy with MTX.
Opposing causal effects of testosterone on sleep in males and females: evidence from a large cohort and bidirectional Mendelian randomization.
Zhu X, Zhang X, Xiang J … +1 more , Jiang C
Steroids · 2026 May · PMID 42218926 · Publisher ↗
OBJECTIVE: To integrate observational and bidirectional Mendelian randomization (MR) analyses to assess the bidirectional causal pathways between total testosterone levels and sleep traits (sleep duration and insufficien...
OBJECTIVE: To integrate observational and bidirectional Mendelian randomization (MR) analyses to assess the bidirectional causal pathways between total testosterone levels and sleep traits (sleep duration and insufficient sleep) in males and females. METHOD: Data from NHANES (2011-2016) were analyzed using weighted logistic regression, subgroup, and threshold analyses. MR was applied to assess causality using genetic instruments. RESULTS: In a cohort of 11,566 participants, observational analyses revealed that elevated total testosterone levels were associated with reduced sleep duration and an increased risk of sleep insufficiency in men. This finding was partially corroborated by Mendelian randomization (MR) analysis, which genetically confirmed a causal effect of higher testosterone on reduced sleep duration in men. In women, both observational and MR analyses consistently demonstrated that higher testosterone levels were associated with a decreased risk of sleep insufficiency. Conversely, neither observational nor MR analyses detected a significant effect of sleep insufficiency or sleep duration on testosterone levels in the overall population. Although an observational association suggested that sleep insufficiency might lower testosterone levels in women, this finding was not supported by MR evidence for a causal relationship. CONCLUSION: In conclusion, our integrated observational and Mendelian randomization analyses suggest a sex-specific causal influence of testosterone on sleep patterns: it reduces sleep duration in men while protecting against sleep insufficiency in women. No evidence was found for reverse causation, indicating that sleep traits do not appear to influence testosterone levels in either sex.
Synthesis and cytotoxicity evaluation of steroidal 17β-hydroxy-17α-methylisoxazoles.
Krech A, Aleksandrova A, Mekhtiev A … +11 more , Timoshenko O, Kugaevskaya E, Zavialova M, Scherbakov K, Chernysheva A, Sorokin D, Scherbakov A, Tsybruk T, Grabovec I, Zhabinskii V, Khripach V
Steroids · 2026 May · PMID 42214712 · Publisher ↗
The aim of this study was to develop an approach to the synthesis of 17β-hydroxy-17α-methylisoxazoles and to evaluate their cytotoxic effects against prostate cancer cell lines. The key reaction in their synthesis was th...
The aim of this study was to develop an approach to the synthesis of 17β-hydroxy-17α-methylisoxazoles and to evaluate their cytotoxic effects against prostate cancer cell lines. The key reaction in their synthesis was the addition of a dianion generated from ethyl acetoacetate and butyllithium to androstenolone. Subsequent stages included the reaction of the intermediate β-hydroxyketone with hydroxylamine to form an isoxazole heterocycle, as well as manipulations with protecting groups. The cytotoxicity of the obtained compounds was studied using hormone-sensitive and hormone-independent prostate and breast carcinoma cell lines. It was found that 17β-hydroxy-17α-methylisoxazoles exerted a more pronounced inhibitory effect on LNCaP cells in comparison with abiraterone, while only minor cytotoxicity was observed toward PC3, MCF-7, and MDA-MB-231 cells. Analysis of the effects of the compounds on cell cycle progression in LNCaP cells demonstrated that they induced cell cycle arrest in the G0/G1 phase. Compound 4 (17α-(Isoxazol-3-ylmethyl)-androst-5-en-3β,17β-diol) suppressed the activity of key signaling pathways (AKT, S6K, ERKs) in LNCaP cells. Binding analysis of the studied compounds to human CYP17A1 revealed a weak spectral response, suggesting that effective binding does not occur in the active site and their mechanism of action is likely unrelated to CYP17A1 inhibition. The steroidal 17β-hydroxy-17α-methylisoxazoles are the basis for the development of new drugs that regulate the activity of kinase signaling pathways in tumor cells.
Two new furostanol saponins from Reineckia carnea.
Wang J, Huang ZH, Guo YX … +2 more , Li HZ, Hao Q
Steroids · 2026 May · PMID 42214711 · Publisher ↗
Two new furostanol saponins, (25S)-22-O-methoxy-5β-furostan-1β,2β,3β,4β,5β,6β,22ξ, 26-octaol-26-O-β-d-glucopyranoside (1) and (25S)-22-O-methoxy-26-O-β-d-glucopyranosyl-5β-furostan-1β,2β,3β,22ξ, 26-pentol-1-O-β-d-xylopyr...
Two new furostanol saponins, (25S)-22-O-methoxy-5β-furostan-1β,2β,3β,4β,5β,6β,22ξ, 26-octaol-26-O-β-d-glucopyranoside (1) and (25S)-22-O-methoxy-26-O-β-d-glucopyranosyl-5β-furostan-1β,2β,3β,22ξ, 26-pentol-1-O-β-d-xylopyranoside (2) were isolated from the whole plant of Reineckia carnea (Andr.) Kunth along with seven known compounds (3-9). The structures of the new saponins were elucidated by detailed analysis of their NMR spectra, chemical evidence and comparison with spectral data of known compounds. Based on the chemical structural characteristics, functional group substitution rules, sugar chain connection methods of the two new furostanol saponins, as well as the natural biogenic synthesis and evolution rules of steroid saponins, an in-depth analysis of the possible biogenetic relationship were conducted. Compound 4, 6, and 9 were obtained for the first time from the Reineckia genus. In addition, the cytotoxic activities in U87-MG and MCF-7 tumor cells of the isolated compounds (1-9) were determined by the MTT method. The results showed that Compound 4 had inhibitory effects on U87-MG cells and MCF-7 cells, with IC values of 35.21 μM and 28.26 μM, respectively.
Efficient synthesis of 15α-hydroxysteroid derivatives by Fusarium redolens.
Sun T, Wang Y, Chen X … +6 more , Zhang R, Lei Y, Feng J, Wang M, Wu Q, Zhu D
Steroids · 2026 May · PMID 42178004 · Publisher ↗
Microbial hydroxylation of steroids at specific positions offers a sustainable and selective strategy for the synthesis of pharmacologically valuable derivatives. Through microorganism screening, the strain Fusarium redo...
Microbial hydroxylation of steroids at specific positions offers a sustainable and selective strategy for the synthesis of pharmacologically valuable derivatives. Through microorganism screening, the strain Fusarium redolens exhibited the highest catalytic efficiency toward androst-4-en-3,17-dione (AD) and enabled the selective synthesis of 15α-hydroxylated derivatives. Under optimized transformation conditions, 10 g/L of AD was efficiently converted into 15α-hydroxy-AD or 11α,15α-dihydroxy-AD with high titers of 7.3 g/L and 7.1 g/L, respectively. The space-time yield (STY) for 15α-hydroxy-AD was 4.9 g/L/d, while the STY for 11α,15α-dihydroxy-AD was 1.1 g/L/d. By controlling the transformation time, 15α-hydroxy-AD and 11α,15α-dihydroxy-AD were obtained with isolated yields of 61.5% and 57.6%, respectively. The dihydroxylation proceeded via a sequential pathway, with initial C15 hydroxylation followed by subsequent C11 hydroxylation. Transcriptomic analysis suggested that both hydroxylation steps might be catalyzed by a cytochrome P450 CYP-1. Moreover, F. redolens displayed broad substrate tolerance toward various steroidal compounds, and several previously unreported 15α-hydroxysteroid derivatives were obtained, highlighting its potential as a versatile biocatalyst for expanding the diversity of hydroxylated steroids. These results demonstrate the promising application of F. redolens as an efficient biocatalytic platform for the selective functionalization of steroid molecules.
Synthesis and biological evaluation of new ergosterol pyridine derivatives as potential anticancer agents.
Liang JJ, Chen XF, Liu XJ … +6 more , Wang C, Wang JH, Yu S, Chang X, Chen H, Deng ZS
Steroids · 2026 May · PMID 42167565 · Publisher ↗
A series of novel ergosterol pyridine derivatives were synthesized via a three-component reaction and their antiproliferative activity was preliminarily evaluated against two human cancer cell lines. Structure-activity r...
A series of novel ergosterol pyridine derivatives were synthesized via a three-component reaction and their antiproliferative activity was preliminarily evaluated against two human cancer cell lines. Structure-activity relationship (SAR) studies revealed that the pyridine ring is more favorable than the phenyl ring for enhancing biological activity. Among them, Compound 5 g displayed the most potent antiproliferative activity against MDA-MB-231 cells (IC = 9.28 μM), surpassing that of ergosterol (IC > 32 μM). Further mechanistic studies revealed that compound 5 g inhibited colony formation without altering intracellular Ca levels. Molecular docking and molecular dynamics simulations revealed that compound 5 g likely binds to ACSL1, a target of ergosterol, primarily through a key hydrogen bond with GLN-155.These results suggest that compound 5 g has potential for further modification and development.
Exploration of steroidal alkaloids: Integrating pharmacognosy, chemoinformatics and artificial intelligence for application diversification.
Patil S, Mulik M, Eknure C … +1 more , Bachhav Y
Steroids · 2026 May · PMID 42167564 · Publisher ↗
Steroidal alkaloids are a structurally diverse class of nitrogen-containing natural products with strong pharmacological potential, including anticancer, anti-inflammatory, and neuroprotective activities. Despite their t...
Steroidal alkaloids are a structurally diverse class of nitrogen-containing natural products with strong pharmacological potential, including anticancer, anti-inflammatory, and neuroprotective activities. Despite their therapeutic potential, clinical translation is hindered by their structural complexity, low natural abundance, and extraction challenges. This review presents an integrated framework that bridges traditional pharmacognosy with advanced phytochemical separation, chemoinformatics, and AI-driven technologies that aid in the discovery and optimization of leads. The pharmacognostic foundation and application of high-resolution separation techniques for steroidal alkaloids have been highlighted. Chemoinformatic tools such as 3D-QSAR (CoMFA/CoMSIA), molecular docking, and pharmacophore modelling have been critically examined for their utility in predicting drug likeness and binding affinities against therapeutically relevant targets. Beyond therapeutic applications, SA holds potential in agrochemical, industrial, and biotechnological domains, although issues related to extraction, standardization, formulation, and clinical deployment persist. By integrating traditional pharmacognostic insights with emerging technologies, this review outlines a comprehensive roadmap for advancing the diverse potential of steroidal alkaloids, while clearly defining current limitations and pointing toward future directions in lead discovery and translational development of steroidal alkaloids.
Synthesis of steroids fused with a pyridine at C11-C12 to accommodate the active site ceiling of cytochrome P450 8B1.
Ho TM, Frydendall EK, Zhou J … +4 more , Offei SD, Arman HD, Scott EE, Yoshimoto FK
Steroids · 2026 May · PMID 42142607 · Publisher ↗
The inhibition of cytochrome P450 8B1 (CYP8B1), the oxysterol 12α-hydroxylase enzyme, is a therapeutic strategy to treat obesity, non-alcoholic fatty liver disease, and diabetes. While nitrogenous heterocycles coordinati...
The inhibition of cytochrome P450 8B1 (CYP8B1), the oxysterol 12α-hydroxylase enzyme, is a therapeutic strategy to treat obesity, non-alcoholic fatty liver disease, and diabetes. While nitrogenous heterocycles coordinating the heme are common P450 inhibitors, previous work revealed that a compound incorporating a pyridine ring at the steroidal C12-position could not access the CYP8B1 active site due to a low ceiling 8.6 Å above the heme. Therefore, in this current study, a pyridine ring was fused at the C11-C12 position of the steroid through the condensation of a C12-ketosteroid intermediate with propargylamine and a copper catalyst in the presence of air. The oxidation states at C3 and C17 were varied as the ketone or the alcohol. These new pyridine steroid analogs bearing a 17-hydroxy group, with the 6.6 Å length from the pyridine to the C6-position, bind in the CYP8B1 active site but do not coordinate the heme iron as anticipated.
Concise synthesis of 7-dehydrocholesterol and 25-hydroxy-7-dehydrocholesterol.
Yue YX, Zhang DJ, Xu JJ … +4 more , Ni HJ, Gu XZ, Li CC, Qiu WW
Steroids · 2026 May · PMID 42142606 · Publisher ↗
7-Dehydrocholesterol (7-DHC) and its hydroxylated product, 25-hydroxy-7-dehydrocholesterol (25-OH-7-DHC), exhibit diverse biological activities and serve as key precursors in the industrial synthesis of vitamin D (VD) an...
7-Dehydrocholesterol (7-DHC) and its hydroxylated product, 25-hydroxy-7-dehydrocholesterol (25-OH-7-DHC), exhibit diverse biological activities and serve as key precursors in the industrial synthesis of vitamin D (VD) and 25-hydroxyvitamin D (25-OH-VD). Consequently, various synthetic routes for 7-DHC and 25-OH-7-DHC have been proposed. Herein, we report a concise and practical synthetic route to 7-DHC (64% total yield) and 25-OH-7-DHC (44% total yield), using commercially available cholesterol and 25-hydroxycholesterol as the starting materials, respectively. The key reaction conditions, including solvent choice, temperature, base, and additive, were systematically investigated and optimized. This innovative synthetic route provides a cost-effective strategy for the potential large-scale production of 7-DHC and 25-OH-7-DHC.
Conessine, a steroidal alkaloid from Holarrhena antidysenterica: Ethnomedical roots, pharmacological insights, and formulation strategies for modern drug development.
Mustafa G, Musa SI, Shinde P … +3 more , Eknure C, Bachhav Y, Paradkar A
Steroids · 2026 May · PMID 42134430 · Publisher ↗
Holarrhena antidysenterica preparations have been used traditionally since ancient times for the treatment of gastrointestinal disorders, parasitic infections, and inflammatory conditions. Conessine is the main steroidal...
Holarrhena antidysenterica preparations have been used traditionally since ancient times for the treatment of gastrointestinal disorders, parasitic infections, and inflammatory conditions. Conessine is the main steroidal alkaloid of Holarrhena antidysenterica, which is commonly associated with its reported biological activities. Current research demonstrates that conessine exhibits antimicrobial activity and inhibits some multidrug efflux pumps responsible for conventional antibiotic resistance. Experimental and computational studies have also reported antiviral, antiplasmodial, anti-inflammatory and neuroprotective activities of conessine. Despite its compelling pharmacological profile, the development of conessine-based therapeutic preparations is limited by challenges related to extraction, formulation, and safety. Overcoming these limitations requires optimization of extraction methods, application of advanced delivery systems, and complementary in silico studies. This review critically explores conessine's ethnomedical background, chemical and biosynthetic insights, analytical methods, pharmacological actions, and formulation approaches to clarify its current scientific status and identify priorities for future research.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe