Effects of Isoxazolyl Steroids on Key Genes of Sonic Hedgehog Cascade Expression in Tumor Cells.

Activation of the Hedgehog (Hh) signaling pathway is often associated with the progression of various types of cancer. The purpose of study was to search for inhibitors of the Hh signaling pathway among eight compounds belonging to the group of isoxazolyl steroids. The evaluation of the effectiveness of the compounds was based on the analysis of their cytotoxicity, effect on the cell cycle, on the expression of key Hh-signaling-pathway genes (Ptch1, Smo, and Gli1) and putative target genes MMP-2 and MMP-9.

Steroidal 21-imidazolium salt derivatives: Synthesis and anticancer activity.

Nitrogen-containing steroids are known as prostate cancer therapeutics. In this work, a series of pregnane derivatives bearing an imidazolium moiety were synthesized using Δ-20-ketones as starting material. An improved approach for the construction of the 20-keto-21-heterocycle-substituted fragment involved the rearrangement of 16,17-epoxides with HCl, followed by reaction of the formed α-chloroketone with 1-substituted imidazoles.

Effects of Lactone- and Ketone-Brassinosteroids of the 28-Homobrassinolide Series on Barley Plants under Water Deficit.

The aim of this work was to study the ability of 28-homobrassinolide (HBL) and 28-homocastasterone (HCS) to increase the resistance of barley ( L.) plants to drought and to alter their endogenous brassinosteroid status. Germinated barley seeds were treated with 0.

Phytohormones as Regulators of Mitochondrial Gene Expression in .

The coordination of activities between nuclei and organelles in plant cells involves information exchange, in which phytohormones may play essential roles. Therefore, the dissection of the mechanisms of hormone-related integration between phytohormones and mitochondria is an important and challenging task. Here, we found that inputs from multiple hormones may cause changes in the transcript accumulation of mitochondrial-encoded genes and nuclear genes encoding mitochondrial (mt) proteins.

Influence of Exogenous 24-Epicasterone on the Hormonal Status of Soybean Plants.

Brassinosteroids (BRs) are key phytohormones involved in the regulation of major processes of cell metabolism that guide plant growth. In the past decades, new evidence has made it clear that BRs also play a key role in the orchestration of plant responses to many abiotic and biotic stresses. In the present work, we analyzed the impact of foliar treatment with 24-epicastasterone (ECS) on the endogenous content of major phytohormones (auxins, salicylic acid, jasmonic acid, and abscisic acid) and their intermediates in soybean leaves 7 days following the treatment.

Endogenous Brassinosteroids Are Involved in the Formation of Salt Resistance in Plants.

The endogenous brassinosteroid (BS) profile was for the first time shown to change in response to salt stress in potato plants. A group of 6-keto-BSs was identified and found to significantly increase in content during salinization in contrast to other groups of hormones examined. A tenfold reduction in the level of endogenous BSs in mutant Arabidopsis thaliana plants with impaired biosynthesis (det2) (or reception (bri1)) of phytosteroids decreased their salt resistance, as evidenced by a lower efficiency of photochemical processes of photosystem II (PSII) and growth inhibition.

Synthesis and Biological Evaluation of New Isoxazolyl Steroids as Anti-Prostate Cancer Agents.

Steroids with a nitrogen-containing heterocycle in the side chain are known as effective inhibitors of androgen signaling and/or testosterone biosynthesis, thus showing beneficial effects for the treatment of prostate cancer. In this work, a series of 3β-hydroxy-5-ene steroids, containing an isoxazole fragment in their side chain, was synthesized. The key steps included the preparation of Weinreb amide, its conversion to acetylenic ketones, and the 1,2- or 1,4-addition of hydroxylamine, depending on the solvent used.

Synthesis and biological activity of 21,22-cyclosteroids and their derivatives.

Synthesis of 21,22-cyclosteroids has been achieved starting from pregnenolone acetate. The key transformation was the Kulinkovich reaction of 17-vinyl steroids with esters. The resulting cyclopropanols were further subjected to three-membered ring-opening under various conditions including to base-, palladium or visible light-promoted isomerization and cross-coupling reaction.

Polymetallic Stress Changes the Endogenous Status of Brassinosteroids and Reduces the Effectiveness of Photochemical Reactions Photosystem II in Barley Plants.

The effect of polymetallic stress (Mn, Cd, Cu, Ni, Zn, Pb, and Al) of different duration and intensity on the endogenous brassinosteroids (BS) content and photochemical activity of photosystem II in barley plants was studied. The content of steroid hormones was determined by a two-stage enzyme immunoassay. It was established for the first time that barley plants responded to polymetallic stress by changing the endogenous content of various phytosteroid groups (24S-methylBS, 24-epiBS, 28-homoBS, B-lactoneBS, and 6-ketoBS).

Structure and Biological Activity of Ergostane-Type Steroids from Fungi.

Mushrooms are known not only for their taste but also for beneficial effects on health attributed to plethora of constituents. All mushrooms belong to the kingdom of fungi, which also includes yeasts and molds. Each year, hundreds of new metabolites of the main fungal sterol, ergosterol, are isolated from fungal sources.

Comparison of Protective Reactions of Rape Seeds to Chloride Salination at Exposure to Epibrassinolide before or during Salt Stress.

We compared the defensive response of rape plants to treatment with 24-epibrassinoldide (10 nM, EBL) before the onset of salt stress (preadaptation stage) and under conditions of chloride salination (150 mM NaCl). It is shown that salt stress inhibits some growth parameters by 30-35%. EBL, regardless of the plant treatment method, showed a pronounced protective effect, first of all, at the level of the assimilating surface, the main photosynthetic pigments, and the photochemical activity of photosystem II.

Terpene Research Is Providing New Inspiration for Scientists.

This current Special Issue of gathers selected communications on terpenes and terpene derivatives, clearly demonstrating the sustained interest in and importance of natural products in this field; fields connected to secondary metabolites; and renewable resources of plant and animal compounds for medicinal, material, supramolecular, and general chemistry research [...

BODIPY Conjugate of Epibrassinolide as a Novel Biologically Active Probe for In Vivo Imaging.

Brassinosteroids (BRs) are plant hormones of steroid nature, regulating various developmental and adaptive processes. The perception, transport, and signaling of BRs are actively studied nowadays via a wide range of biochemical and genetic tools. However, most of the knowledge about BRs intracellular localization and turnover relies on the visualization of the receptors or cellular compartments using dyes or fluorescent protein fusions.

Large Scale Conversion of Trilobolide into the Payload of Mipsagargin: 8--(12-Aminododecanoyl)-8--Debutanoylthapsigargin.

In spite of the impressing cytotoxicity of thapsigargin (), this compound cannot be used as a chemotherapeutic drug because of general toxicity, causing unacceptable side effects. Instead, a prodrug targeted towards tumors, mipsagargin, was brought into clinical trials. What substantially reduces the clinical potential is the limited access to Tg and its derivatives and cost-inefficient syntheses with unacceptably low yields.

A photochemical approach to 18-nor-17β-hydroxymethyl-17α-methylandrost-13-ene steroids.

A photochemical approach to 18-nor-17β-hydroxymethyl-17α-methylandrost-13-ene unit of the long-term metabolites of 17-methylated androgenic anabolic steroids (AAS) is reported. It is based on a visible light-promoted radical decarboxylative alkynylation of steroidal redox-active ester. The developed method was used in synthesis of the long-term metabolite of AAS oxymesterone.

24-Epibrassinolide alleviates the toxic effects of NaCl on photosynthetic processes in potato plants.

Brassinosteroids are promising agents for alleviating the negative effects of salinity on plants, but the mechanism of their protective action is far from being understood. We investigated the effect of pretreatment with 24-epibrassinolide (24-EBL) on the photosynthetic and physiological parameters of potato plants under progressive salinity stress caused by root application of 100 mM NaCl. Salinity clearly inhibited primary photosynthetic processes in potato plants by reducing the contents of photosynthetic pigments, photosynthetic electron transport and photosystem II (PSII) maximal and effective quantum yields.

Growing Importance of Natural Products Research.

Natural products and preparations based on them play a stable and ever-increasing role in human and veterinary medicine, agriculture, in food and the cosmetic industry, and in other increasing numbers of fields. [..

Biological Evaluation of a New Brassinosteroid: Antiproliferative Effects and Targeting Estrogen Receptor α Pathways.

Brassinosteroids (BS), a class of plant-specific steroid hormones, are considered as new potential anticancer agents for the treatment of tumors of different origin, including hormone-dependent cancers. Effects of a synthetic brassinosteroid BS4 ((22R,23R,24R)-22,23-dihydroxy-24-methyl-B-homo-7-oxa-5α-cholest-2-en-6-one ((3aS,7aR,7bS,9aS,10R,12aS,12bS)-10-[(2S,3R,4R,5R)-3,4-dihydroxy-5,6-dimethylheptan-2-yl]-7a,9a-dimethyl-1,3a,4,7,7a,7b,8,9,9a,10,11,12,12a,12b-tetradecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one)) on hormone-dependent breast cancer cells and normal epithelial cells and its impact on the estrogen receptor signaling were evaluated. Cytotoxicity was assessed by MTT-test; expression of estrogen receptor α and survivin was measured by immunoblotting.

Brassinosteroids application induces phosphatidic acid production and modify antioxidant enzymes activity in tobacco in calcium-dependent manner.

Brassinosteroids (BRs) are steroid hormones regulating various aspects of plant metabolism, including growth, development and stress responses. However, little is known about the mechanism of their impact on antioxidant systems and phospholipid turnover. Using tobacco plants overexpressing H/Cavacuolar Arabidopsis antiporter CAX1, we showed the role of Ca ion balance in the reactive oxygen species production and rapid phosphatidic acid accumulation induced by exogenous BR.

The Endogenous Brassinosteroid Content and Balance in Potato Microclones Is Determined by Organ Specificity and the Variety Ripening Term.

The brassinosteroid (BS) profiles in shoots and roots of the potato plants were shown to be organ-specific and dependent on the term of variety ripening. The amount of all studied groups of steroid phytohormones proved to be an order of magnitude higher in roots than in shoots. In roots, the brassinosteroid lactones predominated, while in shoots, their biogenetic precursors, 6-ketones, were prevailing.

Enantioselective catalytic approach to the C23-C28 subunit of 24α-methyl steroids.

Enantioselective synthesis of C23-C28 subunit of campestane steroids based on catalytic methods is reported. The synthesis was started from (S)-2-isopropyl-4-nitrobutan-1-ol, which is easily accessible by the reaction between isovaleraldehyde and nitroethylene catalyzed by only 2% of (S)-trimethylsilyldiphenylprolinol. Removal of one "extra" carbon from the nitroalcohol was achieved by Ni-catalyzed hydrodecarboxylation of the redox-active ester intermediate.

Seed germination, respiratory processes and phosphatidic acid accumulation in Arabidopsis diacylglycerol kinase knockouts - The effect of brassinosteroid, brassinazole and salinity.

Using Arabidopsis thaliana wild type (WT) plants and diacylglycerol kinase knockouts (single mutants - dgk3, dgk1, dgk6; double mutants - dgk3dgk7, dgk5dgk6, dgk1dgk2) we observed that the inhibitor of brassinosteroid (BR) biosynthesis, brassinazole (BRZ), drastically decreased germination of dgk mutants under salt stress, while BRZ co-administration with 24-epibrassinolide (EBL) partially improved germination rates. We also observed a statistically significant decrease in alternative and cytochrome respiratory pathways in response to BRZ treatment under salinity conditions. We showed that production of the lipid second messenger phosphatidic acid (PA) is impaired in dgk mutants in response to EBL treatment and inhibitor of diacylglycerol kinase (DGK) - R59022.

Regio- and stereoselective C-H functionalization of brassinosteroids.

Late stage CH functionalization is a powerful tool for modification of natural compounds. Herein we report that the rhodium-catalyzed reaction of brassinosteroids with aryloxysulfonamides proceeds regio- and stereoselectively at C15 position. The derivative obtained from 24-epibrassinolide was easily transformed to the conjugate with a BODIPY dye bearing unaffected functional groups of the native brassinosteroid.

New azole derivatives of [17(20)E]-21-norpregnene: Synthesis and inhibition of prostate carcinoma cell growth.

A number of isoxazole, 1,2,3-triazole, tetrazole, and 1,2,4-oxadiazole derivatives of [17(20)E]-21-norpregnene comprising 3β-hydroxy-5-ene and 3-oxo-4-ene fragments were prepared. Among the key steps for the synthesis of isoxazoles, 1,2,3-triazoles, and tetrazoles were (i) 1,3-dipolar cycloaddition of nitrile oxides or azides to acetylenes or nitriles and ii) dehydration of 17β-hydroxy-17α-methylene-azoles to [17(20)E]-21-norpregnene derivatives. 1,2,4-Oxadiazoles were prepared through the formation of acetimidamides.

The Priming of Potato Plants Induced by Brassinosteroids Reduces Oxidative Stress and Increases Salt Tolerance.

This is the first study to show that brief pretreatment of potato plants with two brassinosteroids differing in structure causes in plants the ability to react to delayed salt stress by accumulation of compounds with antioxidant activity and by increased salt tolerance.