Design,Synthesis and Biological Evaluation of Steroidal Glycoconjugates as Potential Antiproliferative Agents

To systematically evaluate the impact of neoglycosylation upon the anticancer activities and selectivity of steroids, four series of neoglycosides of diosgenin, pregnenolone, dehydroepiandrosterone and estrone were designed and synthesized according to the neoglycosylation approach. The structures of all the products were elucidated by NMR analysis, and the stereochemistry of C20-MeON-pregnenolone was confirmed by crystal X-ray diffraction. The compounds′ cytotoxicity on five human cancer cell lines was evaluated using a Cell Counting Kit-8 assay, and structure–activity relationships (SAR) are discussed. 2-deoxy-d -glucoside 5 k displayed the most potent antiproliferative activities against HepG2 cells with an IC₅₀ value of 1.5 μM. Further pharmacological experiments on compound 5 k on HepG2 cells revealed that it could cause morphological changes and cell-cycle arrest at the G0/G1 phase and then induced the apoptosis, which might be associated with the enhanced expression of high-mobility group Box 1 (HMGB1). Taken together, these findings prove that the neoglycosylation of steroids could be a promising strategy for the discovery of potential antiproliferative agents.     

Defensive steroids from a carrion beetle (Silpha novaboracensis)

Two novel steroids, 3,7-dihydroxy-14-pregn-4-en-15,20-dione (1) and 3,7, 20-trihydroxy-14-pregn-4-en-15-one (4), have been characterized from the rectal gland ofSilpha novaboracensis (Coleoptera: Silphidae). Judging from the function of comparable pregnanes in another species ofSilpha, the compounds may play an antipredator role.Paper No. 81 of the seriesDefense Mechanisms of Arthropods. Paper No. 80 is Eisner, T., Deyrup, M., Jacobs, R., and Meinwald, J.,J. Chem. Ecol. 12:1407–1415.     

Serotonin-1B receptor activity and expression modulate the aggression-stimulating effects of adolescent anabolic steroid exposure in hamsters.

Repeated high dose (5.0 mg/kg) anabolic-androgenic steroid (AAS) exposure during adolescence stimulates offensive aggression in male Syrian hamsters. These studies examined whether AAS-induced aggression was regulated by the activity of serotonin (5HT) type-1B receptors and correlated with altered 5HT1B expression. AAS-treated hamsters were tested for offensive aggression following the administration of the 5HT1B agonist anpirtoline (0.125-0.5 mg/kg). Anpirtoline dose-dependently reduced select components of the AAS-induced aggressive response, with significant reductions observed at 0.25 mg/kg. Aggressive, AAS-treated hamsters showed significant decreases in the area covered by 5HT1B-containing neuronal puncta and increases in the number of 5HT1B-containing neuronal somata in select brain regions implicated in aggression control. Together, these data support a role for site-specific alterations in 5HT1B signaling and expression in adolescent AAS-induced aggression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tandem mass spectrometry in the study of fatty acids,bile acids,and steroids

Over the last 50 years, the mass spectrometry of lipids has evolved to become one of the most mature techniques in biomolecule analysis. Many volatile and non-polar lipids are directly amenable to analysis by gas-chromatography-mass spectrometry (GC-MS), a technique that combines the unsurpassed separation properties of gas-chromatography with the sensitivity and selectivity of electron ionization mass spectrometry. Less volatile and/or thermally labile lipids can be analyzed by GC-MS, following appropriate sample derivatization. However, many complex lipids are not readily analyzed by GC-MS, and it is these molecules that are the subject of the current review. Since the early 1970s, there have been three outstanding developments in mass spectrometry that are particularly appropriate in lipid analysis; i.e., the introduction of (i) fast atom bombardment (FAB); (ii) electrospray (ES); and (iii) tandem mass spectrometry (MS/MS). The FAB and ES ionization techniques will be discussed in relation to MS/MS, and examples of their application in biochemical studies will be presented. The review will concentrate on the analysis of fatty acids, bile acids, steroid conjugates, and neutral steroids.     

甾醇及其衍生物的质谱学规律（Ⅲ）5α－饱和甾核－甾醇乙酸酯、4－甲基－5α－饱和甾核－甾醇乙酸酯和△~4－3－甾酮的质谱特征

在研究海洋甾类化合物的过程中，本文总结了５α－饱和甾核－甾醇乙酸酯、４－甲基－５α－饱和甾核－甾醇乙酸酯和△４－３－甾酮的质谱中最重要碎片峰的裂解机理和这些甾美化合物的质谱学规律。     

Overcoming Steroid Resistance in Pediatric Acute Lymphoblastic Leukemia—The State-of-the-Art Knowledge and Future Prospects

Acute lymphoblastic leukemia (ALL) is the most common malignancy among children. Despite the enormous progress in ALL therapy, resulting in achieving a 5-year survival rate of up to 90%, the ambitious goal of reaching a 100% survival rate is still being pursued. A typical ALL treatment includes three phases: remission induction and consolidation and maintenance, preceded by a prednisone prephase. Poor prednisone response (PPR) is defined as the presence of ≥1.0 × 10⁹ blasts/L in the peripheral blood on day eight of therapy and results in significantly frequent relapses and worse outcomes. Hence, identifying risk factors of steroid resistance and finding methods of overcoming that resistance may significantly improve patients’ outcomes. A mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK-ERK) pathway seems to be a particularly attractive target, as its activation leads to steroid resistance via a phosphorylating Bcl-2-interacting mediator of cell death (BIM), which is crucial in the steroid-induced cell death. Several mutations causing activation of MAPK-ERK were discovered, notably the interleukin-7 receptor (IL-7R) pathway mutations in T-cell ALL and rat sarcoma virus (Ras) pathway mutations in precursor B-cell ALL. MAPK-ERK pathway inhibitors were demonstrated to enhance the results of dexamethasone therapy in preclinical ALL studies. This report summarizes steroids’ mechanism of action, resistance to treatment, and prospects of steroids therapy in pediatric ALL.     

微生物甾体C11羟化反应的研究现状

羟化反应是甾体微生物转化反应中最重要的反应.介绍了甾体C11羟化的反应机理,并从增加底物溶解性,改善细胞通透性及新型转化系统等方面对微生物C11羟化的新工艺和新技术进行了综述,概述了近五年以来甾体C11羟化的研究现状.在甾体新型转化工艺方面,着重介绍了双液相体系、固定化技术、静息细胞法、多菌协同转化等技术.     

Plasticity in anterior hypothalamic vasopressin correlates with aggression during anabolic-androgenic steroid withdrawal in hamsters.

In hamsters, adolescent anabolic-androgenic steroid (AAS) exposure facilitates offensive aggression, in part by altering the development and activity of anterior hypothalamic arginine vasopressin (AH-AVP). This study assessed whether these effects were lasting by examining aggression and AH-AVP during AAS withdrawal. Adolescent hamsters administered AAS were tested as adults for aggression at 1, 4, 11, 18, or 25 days of withdrawal, sacrificed the following day, and examined for AH-AVP afferent innervation using immunohistochemistry. Through Day 12 of withdrawal, aggression and AVP were significantly higher in AAS-treated hamsters than in controls. These differences were no longer observable by Day 19 of withdrawal, at which point the behavior and neurobiology of AAS-treated hamsters reverted to that observed in controls. These data indicate that adolescent AAS exposure has short-term, reversible effects on both aggression and AH-AVP, correlating AH-AVP with the aggressive/nonaggressive behavioral phenotype during AAS withdrawal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)