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Abstract Although structurally simple, viroids can trigger numerous changes in host plants and cause loss of yield in agronomically important crops. This study investigated changes in the endogenous status of phytohormones and antioxidant enzyme activity in Solanum tuberosum cv. Désirée in response to Potato spindle tuber viroid (PSTVd) infection. Phytohormone analysis showed that the content of endogenous jasmonic acid (JA) and its precursor cis -OPDA significantly increased in leaves, while the content of castasterone (CS) increased in both leaves and tubers of systemically infected plants compared to mock-inoculated control plants at 8 weeks post-inoculation. The indole-3-acetic acid content moderately increased only in tubers, while no differences in salicylic acid and abscisic acid content were observed between infected and control plants. Changes in endogenous phytohormone content were associated with upregulated expression of genes involved in the biosynthesis of JA and brassinosteroids, and the metabolism of auxins. Additionally, PSTVd infection provoked overproduction of hydrogen peroxide, which coincided with increased activity of guaiacol peroxidase in leaves and ascorbate peroxidase in potato tubers. The activity of catalase decreased in leaves, while superoxide dismutase activity remained steady regardless of the treatment and organ type. Total ascorbate and glutathione did not change significantly, although a shift towards oxidized forms was observed. Results suggest the existence of organ-specific differences in phytohormone and antioxidative responses in potato upon PSTVd infection. Possible effects of the observed changes on symptom development are discussed. [ABSTRACT FROM AUTHOR]

Progesterone is a mammalian hormone that has also been discovered in plants but its physiological function in plants is not explained. Experiments using inhibitors of progesterone synthesis and binding would be useful in studies on the significance of this compound in plants. Until now, trilostane and mifepristone have been used in medical sciences as progesterone biosynthesis and binding inhibitors, respectively. We tested these synthetic steroids for the first time in plants and found that they reduced the content of progesterone in wheat. The aim of further experiments was to answer whether the potential disturbances in the production/binding of progesterone, influence resistance to environmental stress (drought) and the development of wheat. Inhibitors and progesterone were applied to plants via roots in a concentration of 0.25–0.5 mg/l water. Both inhibitors lowered the activity of CO 2 binding enzyme (Rubisco) in wheat exposed to drought stress and trilostane additionally lowered the chlorophyll content. However, trilostane-treated plants were rescued by treatment with exogenous progesterone. The inhibitors also modulated the development of winter wheat, which indicated the significance of steroid regulators and their receptors in this process. In this study, in addition to progesterone and its inhibitors, brassinosteroid (24-epibrassinolide) and an inhibitor of biosynthesis of brassinosteroids were also applied. Mifepristone inhibited the generative development of wheat (like 24-epibrassinolide), while trilostane (like progesterone and an inhibitor of biosynthesis of brassinosteroids) stimulated the development. We propose a model of steroid-induced regulation of the development of winter wheat, where brassinosteroids act as inhibitors of generative development, while progesterone or other pregnane derivatives act as stimulators. [ABSTRACT FROM AUTHOR]

Highlights: [•] New monohydroxylated brassinosteroid analogues were synthesized. [•] Biological activities of these derivatives were studied. [•] All derivatives were subjected to docking studies using AutoDock Vina. [•] The molecular docking showed interesting binding affinity of some compounds prepared to kinase receptor BRI1. [ABSTRACT FROM AUTHOR]

A series of phenyl analogues of brassinosteroids was prepared via alkene cross-metathesis using commercially available styrenes and 24-nor-5α-chola-2,22-dien-6-one. All derivatives were successfully docked into the active site of BRI1 using AutoDock Vina. Plant growth promoting activity was measured using the pea inhibition biotest and Arabidopsis root sensitivity assay and then was compared with naturally occuring brassinosteroids. Differences in the production of plant hormone ethylene were also observed in etiolated pea seedlings after treatment with the new and also five known brassinosteroid phenyl analogues. Antiproliferative activity was also studied using normal human fibroblast and human cancer cell lines. [ABSTRACT FROM AUTHOR]

Abstract: Sixteen platinum(II) complexes of estrone and estradiol were synthesized in this work to evaluate their cytotoxic activity against several cancer cell lines including estrogen dependent and independent ones. The synthesis of all the complexes was done in three steps. The reaction of steroids with dibromoalkanes was followed by a reaction of the bromoalkyl steroids with 2-(aminomethyl)pyridine or 2-(2-aminoethyl)pyridine. The last step was a reaction of steroidal diamino ligands with potassium tetrachloroplatinate to obtain the desired platinum(II) complexes. Cytotoxicity assays showed that most of the complexes prepared are active against the cancer cell lines used—CEM, U-2 OS, MCF7, MCF7 AL, MDA-MB-468, BT-474, BT-549, and BJ fibroblasts. The six-membered platinum complexes are more active than five-membered ones. [Copyright &y& Elsevier]

Plant hormone brassinosteroids (BRs) have multiple important functions in plants. They have also been found to exhibit anti-tumor, anti-angiogenic and anti-proliferative activity. The experimental part of this article describes the effects of BR biosynthetic precursors on prostate cancer cells. The experiments were performed with LNCaP and DU-145 prostate cancer cell lines. These were cultivated and treated with tested BRs in different concentrations and time intervals. The tested compounds were found to affect cell viability, nuclear receptor expression, cell cycle and apoptosis in the tumor cells. IC 50 concentrations were determined based on MTT test and the two most active compounds (cathasterone and 6-oxocampestanol) were used in the next experiments. Cathasterone was the most effective of all tested compounds and effectively inhibited integrity of cell spheres. It was found that both BRs had no significant effect on the cell cycle in LNCaP at IC 50 concentration, while in DU-145 a significant block in G 0 /G 1 phase after the BR treatment was observed. The effect of BRs on the nuclear steroid receptors was manifested by changes in their expression and localization. BRs demonstrated their significant effect on prostate cancer cells and the compounds have potential used in anticancer drug research and cancer treatment. Image 1 • Biosynthetic BR precursors have effects on prostate cancer cells and indicate potential use in cancer drug development. • Tumor cell viability was most effectively inhibited by cathasterone and 6-oxocampestanol with a broad therapeutic window. • The impact of BRs on the nuclear receptors for steroid hormones was manifested by a change in their expression. [ABSTRACT FROM AUTHOR]

The purpose of experiments was to describe the alterations of content of steroid regulators (brassinosteroids, progesterone) during cold hardening of winter wheat. Further we studied physiological and biochemical changes induced by these steroids in cold hardened winter wheat together with estimation of plant frost tolerance. The endogenous brassinosteroid content was elevated in winter wheat during cold hardening while level of progesterone was lowered. A higher content of brassinosteroids (but not progesterone) was connected to better frost tolerance of winter wheat cultivars. Plant supplementation with brassinosteroid (24-epibrassinolide) and progesterone before cold hardening reduced frost damage. Tests with the inhibitors of the biosynthesis of brassinosteroids and progesterone suggested that these steroids are one of players in regulating the antioxidant system in winter wheat during cold hardening. Their role in regulating the expression of Rubisco or the Rubisco activase gene was less clear. Steroid regulators did not affect the content of the stress hormone ABA. Model studies of the membranes, made on a Langmuir bath, showed an increase in the value of the parameter describing differences in membrane compressibility (resulting from stronger interactions among the molecules in the monolayers). This suggests that 24-epibrassinolide and progesterone enter into the lipid layer and - in a similar way to sterols – stabilise the interaction among lipids. It may be significant step for better frost tolerance. The use of steroid regulators (especially brassinosteroids) as agrochemicals improving frost tolerance of winter cereals will be discussed. • Content of brassinosteroids (BR) increased in winter wheat during cold hardening. • Progesterone (P) content decreased in winter wheat during cold hardening. • Higher BR content characterised cultivars with higher frost tolerance. • BR and P were incorporated into the lipid layer and stabilized it. • BR and P regulated the activity of the SOD enzyme. [ABSTRACT FROM AUTHOR]

Abstract This study focused on the idea that the toxic effect of zearalenone (ZEA) and the protective actions of the brassinosteroid - 24-epibrassinolide (EBR) as well as selenium are dependent on its accumulation in chloroplasts to a high degree. These organelles were isolated from the leaves of oxidative stress-sensitive and stress-tolerant wheat cultivars that had been grown from grains that had been incubated in a solution of ZEA (30 μM), Na 2 SeO 4 (Se, 10 μM), EBR (0.1 μM) or in a mixture of ZEA with Se or EBR. Ultra-high performance liquid chromatography techniques indicated that ZEA was adsorbed in higher amounts in the chloroplasts in the sensitive rather than tolerant cultivar. Although the brassinosteroids and Se were also accumulated in the chloroplasts, higher levels were only found in the tolerant cultivar. The application of EBR increased the homocastasterone content, especially in the chloroplasts of the tolerant plant and after the addition of ZEA. The presence of both protectants caused a decrease in the ZEA content in studied organelles and resulted in diminishing of the oxidative stress (i.e. changes in the activity of the antioxidative enzymes). Moreover, a recovery of photosystem II and decrease in the negative impact of ZEN on Hsp 90 transcript accumulation was observed in plants. Highlights • Zearalenone, brassinosteroids and selenium were accumulated in chloroplasts. • 24-Epibrassinolide and Se absorption in chloroplasts was stimulated by zearalenone. • 24-Epibrassinolide and Se absorption in chloroplast decreased of zearalenone content. • Defense mechanism against zearalenone involved protection of PSII. [ABSTRACT FROM AUTHOR]

Estrogen receptor alpha (ER) is a key biomarker for breast cancer, and the presence or absence of ER in breast and other hormone-dependent cancers decides treatment regimens and patient prognosis. ER is activated after ligand binding - typically by steroid. 2682 steroid compounds were used in a molecular docking study to identify novel ligands for ER and to predict compounds that may show anticancer activity. The effect of the most promising compounds was determined by a novel luciferase reporter assay. Two compounds, 7 and 12 , showing ER inhibitory activity comparable to clinical inhibitors such as tamoxifen or fulvestrant were selected. We propose that the inhibitory effect of compounds 7 and 12 on ER is related to the presence of a double bond in their D -ring, which may protect against ER activation by reducing the electron density of the keto group, or may undergo metabolism leading to an active compound. Western blotting revealed that compound 12 decreased the level of ER in the breast cancer cell line MCF7, which was associated with reduced expression of both isoforms of the progesterone receptor, a well-known downstream target of ER. However, compound 12 has a different mechanism of action from fulvestrant. Furthermore, we found that compound 12 interferes with mitochondrial functions, probably by disrupting the electron transport chain, leading to induction of the intrinsic apoptotic pathway even in ER-negative breast cancer cells. In conclusion, the combination of computational and experimental methods shown here represents a rapid approach to determine the activity of compounds towards ER. Our data will not only contribute to research focused on the regulation of ER activity but may also be useful for the further development of novel steroid receptor-targeted drugs applicable in clinical practice. [Display omitted] • Virtual screening library consisting of 2,682 steroid compounds. • Identification of compound 12 exhibiting an antagonistic effect on ER. • Compound 12 induces apoptosis independently of the ER status of cancer cells. • Compound 12 exerts a dual mechanism of antitumor action. [ABSTRACT FROM AUTHOR]

We report the synthesis and detailed biological study of the synthetic brassinosteroid analog 2α,3α-dihydroxy-6-oxo-5α-androstan-17β-yl N-(tert -butoxycarbonyl)-D,L-valinate (BR4848). The panel of cancer cell lines was used for characterization of its antiproliferative activity, yet had no adverse effects in normal human fibroblasts. In HeLa cells, BR4848-induced apoptosis was accompanied by increase of apoptotic subG 1 cells, PARP-1 and caspase-7 fragmentation, downregulation of Bcl-2 and Mcl-1, an increase in caspase activity and G 2 /M phase cell cycle arrest. Antiproliferative properties of BR4848 were exhibited by inhibition of phosphorylation of Akt, Erk1/2 and FAK. Furthermore, the developed analog exhibited in vitro antiangiogenic activity in human umbilical vein endothelial cells (HUVECs). BR4848-induced apoptosis accompanied with G 2 /M arrest was detected in endothelial cells. BR4848 also inhibited adhesion, tube formation and migration of endothelial cells by inhibition of FAK, Erk 1/2, CDK5, VEGFR2, TNFα-stimulated production of IL-6, angiopoietin-2 and Jagged1. Finally, BR4848 did not modulate the activity nor nuclear translocation of any of the steroid receptors (ERα, ERβ, AR, MR and PR) included in reporter cell-based assays, which excludes the genomic activity of steroid receptors as a contributing factor to the observed biological activities of BR4848. [ABSTRACT FROM AUTHOR]

Structure-activity relationship analysis and profiling of a library of AB-functionalized cholestane derivatives closely related to brassinosteroids (BRs) were performed to examine their antiproliferative activities and activities on steroid hormone receptors. Some of the compounds were found to have strong cytotoxic activity in several human normal and cancer cell lines. The presence of a 3-hydroxy or 3-oxo group and 2,3-vicinal diol or 3,4-vicinal diol moiety were found to be necessary for optimum biological activity, as well as a six-membered B ring. According to the profiling of all steroid receptors in both agonist and antagonist mode, the majority of the cholestanes were weakly active or inactive compared to the natural ligands. Estrogenic activity was detected for two compounds, two compounds possessed antagonistic properties on estrogen receptors and seven compounds showed agonistic activity. Two active cholestane derivatives were shown to strongly influence cell viability, proliferation, cell cycle distribution, apoptosis and molecular pathways responsible for these processes in hormone-sensitive/insensitive (MCF7/MDA-MB-468) breast cancer cell lines. [ABSTRACT FROM AUTHOR]

Abstract: Androstane brassinosteroid analogues with α-azido acid ester groups in position 17β were synthesized from 2α,3α,17β-trihydroxy-5α-androstan-6-one after the protection of the 2α,3α-diols upon treatment with the corresponding α-azido acid and the subsequent deprotection of the diol grouping. Six new castasterone analogues were prepared. The biological activities were evaluated in two bioassays: a rice lamina inclination test and bean second internode bioassays. The activities of the new analogues differ in these two bioassays. [ABSTRACT FROM AUTHOR]