Steroids最新文献

Background

Breast cancer stands as a leading contributor to global cancer-related mortality. Progressing Research and Medical Innovations Elevate Treatment Choices and Results for Breast Cancer. Among these, Peimine, a natural steroid inherent in plants, notably within the Fritillaria species, demonstrates the capability to trigger apoptosis in breast cancer cells through the mitochondrial membrane permeation pathway. Nevertheless, its impact on an appropriate cancer model remains an area necessitating further exploration.

Aim

This study explored the in vivo anticancer effects of peimine on MRMT-1 Cell-line induced breast cancer in rats.

Method

Cancer was induced by the administration of MRMT-1 (6 x 10⁶ cells) cells in the mammary pads of SD rats. The daily drug treatment commenced on day 14 and continued till 39 days. Peimine was administered in two doses (0.24 mg/kg and 0.48 mg/kg p.o) to examine its efficacy in curing breast cancer while tamoxifen was used as standard.

Results

A reduction in tumour size was observed in the peimine-treated groups. Peimine can correct the changed blood cell count in addition to its anti-tumour activity. In peimine-treated rats, imbalanced immune marker IgE, serum oxidative marker, and tissue apoptotic markers like cytochrome c and calcium level were shown to be restored significantly.

Conclusion

Our findings imply that quinine has beneficial effects as an anti-neoplastic medication for breast cancer, most likely through its apoptotic activity. More research is necessary to thoroughly understand their mechanisms of action, ideal dose, and potential side effects.

Hydrocortisone succinate (1) is a synthetic anti-inflammatory drug and key intermediate in the synthesis of other steroidal drugs. This work is based on the fungal biotransformation of 1, using Monascus purpureus and Cunninghamella echinulata strains. Comopound 1 was transformed into four metabolites, identified as hydrocortisone (2), 11β-hydroxyandrost-4-en-3,17-dione (3), Δ¹-cortienic acid (4), and hydrocortisone-17-succinate (5), obtained through side chain cleavage, hydrolysis, dehydrogenation, and oxidation reactions. These compounds have previously been synthesized either chemically or enzymatically from different precursors. Though this is not the first report on the biotransformation of 1, but it obviously is a first, where the biotransformed products of compound 1 have been characterized structurally with the help of modern spectroscopic techniques. It is noteworthy that these products have already shown biological potential, however a more thorough investigation of the anti-inflammatory properties of these metabolites would be of high value. These results not only emphasize upon the immense potential of biotransformation in catalysis of reactions, otherwise not-achievable chemically, but also holds promise for the development of novel anti-inflammatory compounds.

Anabolic-androgenic steroids (AAS) are used widely, but in illegal ways mostly by young men as performance-enhancing and image-enhancing drugs (IPED). long-term usage of AAS, usually in conjunction with other illegal substances, can have extremely detrimental impacts on the reproductive system. The primary goal of this study was to examine any possible detrimental effects of AAS on sex hormone levels, a liver and kidney function in individuals who frequent fitness centers in Iraq-Baghdad. In this research, there are 60 participants (20–37 years old); 30 athletes who visited the different gyms in Baghdad/ Iraq and used AAS such as testosterone, Boldenone, Cybontae, Deca Durabellin; and 30 athletes who did not take any synthetics hormones and serve as control. All participants answered the questionnaire form which included their age, the type of used AAS, when they started to take it, and the total usage number per week. The blood (5 ml) was drawn from every participant to separate the serum. The serum was used to measure some hormones (Testosterone, FSH, LH, prolactin and Estrodiol) and liver and kidney function parameters. The results showed a significantly lower level of testosterone and FSH in the AAS-users’ bodybuilding group compared to the control group. In comparison with the control group, there was a notable rise in the PRL level in the serum of AA users. However, when comparing the serum levels of LH and Estrodiol in the AAS-user group to those in the control group, no discernible variations were seen. AAS users had a significantly higher level of ALT and lower ALP than controls, although there is no difference in AST levels between the two groups. The creatine level was significantly higher in the AAS-user compared to the control group, but not urea. In conclusion, the effects of AAS and other supplements on sex hormones and kidney, liver function, and vary depending on how long they are used, with the effects of AAS being more pronounced. Therefore, there is a need for culturally sensitive measures to prevent steroid abuse among youth.

Betulonic acid benzyl ester 1 has been subjected to a series of structural modifications for the purpose of new triterpenoid synthesis and evaluating for anticancer activity. The one-pot two step synthesis of 2α-(aminomethyl)betulinic acid benzyl ester derivatives 3a–f (yield 46–69 %) was achieved by the Mannich reaction of compound 1 with methyleneiminium salts, generated in situ from N,N-disubstituted bis(amino)methanes 2a–f by the action of acetyl chloride in dichloromethane, and subsequent reduction of aminomethylation products with sodium borohydride. Minor 2β-(aminomethyl) triterpenoids 4c,d,f were also isolated (yield 6–15 %). We found, that the stereoselective reaction of triterpenoid 1 with acetylides, generated at –78 °C from alkynes in the presence of n-BuLi, has been useful and noteworthy as the key step in providing of new alkyne substituted triterpenoids – benzyl 3-alkynyl-3-deoxy-2(3),20(29)-lupadiene-28-oates or 3-deoxy-2(3)-dehydro-28-oxoallobetulin derivative. The new compounds were examined for anticancer activity against the human cell lines (MTT assay). All tested derivatives were non-toxic on human fibroblasts. The 3‐(phenylethynyl)lupa-2(3),20(29)-diene 9 showed selective cytotoxicity on cervical cancer cell lines. Tumor cells death trigged by the most active compound 4f resulted from apoptotic processes. These data make the series of synthesized 2 or 3 substituted lupane derivatives as promising compounds with anticancer potential.

Candida auris, a pathogenic fungus, has posed significant challenges to conventional medical treatments due to its increasing resistance to antifungal agents. Consequently, due to their promising pharmacological properties, there is a compelling interest in exploring novel bioactive compounds, such as phytosterols and triterpenes. This study aimed to conduct virtual screening utilizing computational methods, including ADMET, molecular docking, and molecular dynamics, to assess the activity and feasibility of phytosterols extracted from Cryptostegia grandiflora as potential therapeutic agents. Computational predictions suggest that compounds bearing structural similarities to Fsp³-rich molecules hold promise for inhibiting enzymes and G protein-coupled receptor (GPCR) modulators, with particular emphasis on ursolic acid, which, in its conjugated form, exhibits high oral bioavailability and metabolic stability, rendering it a compelling drug candidate. Molecular docking calculations identified ursolic acid and stigmasterol as promising ligands. While stigmasterol displayed superior affinity during molecular dynamics simulations, it exhibited instability, contrasting with ursolic acid’s slightly lower affinity yet sustained stability throughout the dynamic assessments. This suggests that ursolic acid is a robust candidate for inhibiting the FKBP12 isomerase in C. auris. Moreover, further investigations could focus on experimentally validating the molecular docking predictions and evaluating the efficacy of ursolic acid as an FKBP12 isomerase inhibitor in models of C. auris infection.

Occupancy of prostate cancer (PCa) cell androgen receptors (AR) signals proliferation, therefore testosterone biosynthesis inhibitors and AR antagonists are important PCa treatments. Conversely, androgen mimics (e.g., prednisone) used in management of PCa might cause proliferation. The balance between PCa proliferation and inhibition predicts treatment success. We used in silico molecular modelling to explore interactions between ARs, androgens (testosterone, dihydrotestosterone (DHT)) and drugs used to treat (bicalutamide) and manage (dexamethasone, prednisone, hydrocortisone) PCa. We found that hydrogen (H-) bonds between testosterone, DHT and Arg752, Asn705 and Thr877 followed by ligand binding cleft hydrophobic interactions signal proliferation, whereas bicalutamide antagonism is via Phe764 interactions. Hydrocortisone, dexamethasone and prednisone H-bond Asn705 and Thr877, but not Arg752 in the absence of a water molecule. Studies with a bicalutamide agonist AR mutation showed different amino acid interactions, indicating testosterone and DHT would not promote proliferation as effectively as via the native receptor. However, hydrocortisone and bicalutamide form Arg752 and Asn705 H-bonds indicating agonism. Our results suggest that as PCa progresses the resulting mutations will change the proliferative response to androgens and their drug mimics, which have implications for the treatment of prostate cancer.

Vitamin D dysregulation has been recognized as a factor that may cause or aggravate autoimmunity. Vitamin D deficiency was found to be common in pemphigus vulgaris (PV) in different populations. This study aimed to investigate the vitamin D-VDR pathway in PV in the Tunisian population.

A serological study was carried out to determine the vitamin D status in newly diagnosed PV patients. CYP27B1, CYP24A1 and VDR mRNA expression was assessed using quantitative real-time PCR in peripheral blood mononuclear cells (PBMC) from untreated newly diagnosed and treated PV patients. In addition, a genetic study was accomplished on VDR polymorphisms to investigate the changes in VDR gene expression. Overall, the serological study confirmed the hypovitaminosis D in newly diagnosed PV patients. Vitamin D-VDR pathway gene expression showed downregulation of CYP27B1 and CYP24A1 mRNA in first-discovery patients compared to healthy controls, while VDR mRNA was highly expressed in newly diagnosed PV patients. Moreover, CYP27B1, CYP24A1 and VDR mRNA were significantly upregulated in chronic disease severity groups compared to mild disease groups. The genetic study showed low VDR gene expression in carriers of FokI > CC genotype, which was more frequent among PV patients, and FokI > C-TaqI > C-ApaI > A-polyA > A₁₆ haplotype, suggesting that the VDR gene polymorphisms testing can provide useful information for PV treatment decision-making.

In conclusion, our findings underline the impact of vitamin D-VDR pathway disruption in the PV pathophysiology in Tunisian patients.

Polycystic ovary syndrome (PCOS) represents major endocrine and metabolic disorder among women largely characterized by hyperandrogenism and oligomenorrhea precipitates serious complications such as type 2 diabetes, early atherosclerosis, infertility, and endometrial cancer. Several etiological theories were proposed to define the exact cause of the PCOS, which is characterized, by the hypothalamic-pituitary axis, ovarian morphology, and release of adrenal steroid hormones, metabolic syndrome, and hereditary factors. The review explored the role of dysbiosis and the mechanisms through which microbial dysbiosis can affect PCOS development. In recent time, various research groups highlighted the role of microbial gut dysbiosis associated with obesity as potential etiological factor for the PCOS. In the present review, we reviewed the mechanisms attributed to the microbial dysbiosis and treatment approaches to deal with the situation.

Chemical investigation of the fungus Trichoderma asperellum SCNU-F0048 led to the discovery of two new steroids, ergosta-4,6,8 (14),22-tetraen-3-(3′-methyl-4′-hydroxyl-γ-butenolide) (1) and camphosterol B (2), as well as two known compounds, i.e. stigmasta-4,6,8(14),22-tetraen-3-one (3) and 4-hydroxy-17- methylincisterol (4). Their structures were elucidated by extensive nuclear mangnetic resonance, spectrum analysis and single crystal X-ray diffraction analysis. Bioassay disclosed that compound 1 showed strong cytotoxicity to a panel of tumor cell lines. Moreover, compounds 1 and 2 showed excellent antifungal activity against Penicillium italicum with IC₅₀ values of 0.016 and 0.022 μM, respectively.