Brassinosteroids are a class of plant hormones that regulate a broad range of physiological processes such as plant growth, development and immunity, including the suppression of biotic and abiotic stresses. In this paper, we report the synthesis of new brassinosteroid analogues with a nitrogen-containing side chain and their biological activity on Arabidopis thaliana. Based on molecular docking experiments, two groups of brassinosteroid analogues were prepared with short and long side chains in order to study the impact of side chain length on plants. The derivatives with a short side chain were prepared with amide, amine and ammonium functional groups. The derivatives with a long side chain were synthesized using amide and ammonium functional groups. A total of 25 new brassinosteroid analogues were prepared. All 25 compounds were tested in an Arabidopsis root sensitivity bioassay and cytotoxicity screening. The synthesized substances showed no significant inhibitory activity compared to natural 24-epibrassinolide. In contrast, in low concentration, several compounds (8a, 8b, 8e, 16e, 22a and 22e) showed interesting growth-promoting activity. The cytotoxicity assay showed no toxicity of the prepared compounds on cancer and normal cell lines.

• Klíčová slova
• brassinosteroid, cytotoxicity, nitrogen-containing steroid, organic synthesis, plant bioassay,
• MeSH
• Arabidopsis účinky léků   růst a vývoj   MeSH
• brassinosteroidy chemická syntéza   chemie   farmakologie   MeSH
• dusík chemie   MeSH
• molekulární struktura MeSH
• techniky syntetické chemie * MeSH
• vývoj rostlin účinky léků   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• brassinosteroidy MeSH
• dusík MeSH

Thirteen monohydroxylated brassinosteroids analogues were synthesized and tested for their biological activity in plant and animal systems. The cytotoxic activity of the products was studied using human normal and cancer cell lines with 28-homocastasterone as positive control, their brassinolide type activity was established using the bean second-internode test with 24-epibrassinolide as standard.

• Klíčová slova
• Anticancer activity, Brassinosteroids, Molecular docking, Organic synthesis, Plant bioassays, Receptor kinase BRI1,
• MeSH
• brassinosteroidy aplikace a dávkování   chemická syntéza   MeSH
• cholestanoly aplikace a dávkování   chemická syntéza   MeSH
• cytotoxiny aplikace a dávkování   chemická syntéza   MeSH
• lidé MeSH
• molekulární struktura MeSH
• nádorové buněčné linie MeSH
• proliferace buněk účinky léků   MeSH
• steroidy heterocyklické aplikace a dávkování   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• brassinolide MeSH Prohlížeč
• brassinosteroidy MeSH
• cholestanoly MeSH
• cytotoxiny MeSH
• steroidy heterocyklické MeSH

We have prepared and studied a series of new brassinosteroid derivatives with a p-substituted phenyl group in the side chain. To obtain the best comparison between molecular docking and biological activities both types of brassinosteroids were synthesized; 6-ketones, 10 examples, and B-lactones, 8 examples. The phenyl group was introduced into the steroid skeleton by Horner-Wadsworth-Emmons. The docking studies were carried out using AutoDock Vina 1.05. Plant biological activities were established using different brassinosteroid bioassays in comparison with natural brassinosteroids. Differences in the production of the plant hormone ethylene were also observed in etiolated pea seedlings after treatment with new brassinosteroids. The most active compounds were lactone 8f and 6-oxo derivatives 8c and 9c, their biological activities were comparable or even better than naturally occurring brassinolide. Finally the cytotoxicity of the new derivatives was studied using human normal and cancer cell lines.

• MeSH
• Arabidopsis metabolismus   MeSH
• brassinosteroidy chemie   metabolismus   farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory farmakoterapie   MeSH
• proteinkinasy metabolismus   MeSH
• proteiny huseníčku metabolismus   MeSH
• protinádorové látky chemie   metabolismus   farmakologie   MeSH
• regulátory růstu rostlin metabolismus   MeSH
• simulace molekulového dockingu MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• brassinosteroidy MeSH
• BRI1 protein, Arabidopsis MeSH Prohlížeč
• proteinkinasy MeSH
• proteiny huseníčku MeSH
• protinádorové látky MeSH
• regulátory růstu rostlin MeSH

Synthesis and structure-activity relationship analysis of a two groups of 2,3-seco analogues of brassinosteroids (BRs) were performed to examine their antiproliferative activities. Two steroid skeletons were chosen for the preparation of seco analogues - cholestane and stigmastane. The synthetic strategy consists of multistep reactions and detailed analysis of compounds prepared. We have discovered unpublished behaviour of 2,3-seco-2,3-dihydroxy-6-ketones leading to formation of intramolecular ketal with two new steroidal rings. Their reaction intermediates were also characterized in some cases. All compounds prepared were fully characterized with NMR and MS techniques. Most of compounds were tested for in vitro cytotoxicity on three cancer cell lines (CEM, MCF7, and HeLa) and normal human fibroblasts (BJ). It was discovered that some seco analogues caused apoptosis in cancer cells. The most promising seco derivative 28 proved to have high therapeutic index.

• Klíčová slova
• Apoptosis, Brassinosteroids, Cyclization, Cytotoxicity, Seco analogues, Skeletal modification,
• MeSH
• apoptóza účinky léků   MeSH
• brassinosteroidy chemická syntéza   chemie   farmakologie   MeSH
• HeLa buňky MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky chemická syntéza   chemie   farmakologie   MeSH
• screeningové testy protinádorových léčiv MeSH
• techniky syntetické chemie MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• brassinosteroidy MeSH
• protinádorové látky MeSH

Androstane brassinosteroid analogues with alpha-azido acid ester groups in position 17beta were synthesized from 2alpha,3alpha,17beta-trihydroxy-5alpha-androstan-6-one after the protection of the 2alpha,3alpha-diols upon treatment with the corresponding alpha-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.

• MeSH
• androstany chemická syntéza   chemie   MeSH
• azidy chemie   MeSH
• estery MeSH
• hydroxidy chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• androstane MeSH Prohlížeč
• androstany MeSH
• azidy MeSH
• estery MeSH
• hydroxide ion MeSH Prohlížeč
• hydroxidy MeSH

Three types of 5alpha-androstane and ergostane analogues of brassinolide, containing a fluorine atom in either the 3alpha or the 5alpha positions or in 3alpha and 5alpha positions, were prepared using standard operations (reaction of 3beta-alcohols with (diethylamino)sulfur trifluoride, cleavage of epoxide with HF in py or BF 3.Et 2O). The 5alpha-fluorine was found to affect chemical reactivity (e.g., electrophilic addition to the Delta (2)-double bond) as well as physical properties (e.g., NMR, chromatographic behavior) of the products. Cytotoxicity of the products was studied using human normal and cancer cell lines with 28-homocastasterone as positive control and their brassinolide type activity was established using the bean second-internode test with 24-epibrassinolide as standard. The equivalence of F and OH groups was observed in some of the active compounds. The anticancer and the brassinolide-type activity do not correlate with each other: ergostane derivatives were most active in the former test while androstane derivatives were best in the latter.

• MeSH
• brassinosteroidy MeSH
• buněčné linie MeSH
• cholestanoly chemická syntéza   chemie   farmakologie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• protinádorové látky chemická syntéza   chemie   farmakologie   MeSH
• sloučeniny fluoru chemická syntéza   chemie   farmakologie   MeSH
• steroidy heterocyklické chemická syntéza   chemie   farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• brassinolide MeSH Prohlížeč
• brassinosteroidy MeSH
• cholestanoly MeSH
• protinádorové látky MeSH
• sloučeniny fluoru MeSH
• steroidy heterocyklické MeSH

Winter plants acclimate to frost mainly during the autumn months, through the process of cold acclimation. Global climate change is causing changes in weather patterns such as the occurrence of warmer periods during late autumn or in winter. An increase in temperature after cold acclimation can decrease frost tolerance, which is particularly dangerous for winter crops. The aim of this study was to investigate the role of brassinosteroids (BRs) and BR analogues as protective agents against the negative results of deacclimation. Plants were cold-acclimated (3 weeks, 4 °C) and deacclimated (1 week, 16/9 °C d/n). Deacclimation generally reversed the cold-induced changes in the level of the putative brassinosteroid receptor protein (BRI1), the expression of BR-induced COR, and the expression of SERK1, which is involved in BR signal transduction. The deacclimation-induced decrease in frost tolerance in oilseed rape could to some extent be limited by applying steroid regulators. The deacclimation in plants could be detected using non-invasive measurements such as leaf reflectance, chlorophyll a fluorescence, and gas exchange monitoring.

• Klíčová slova
• 24-epibrassinolide, 28-homocastasterone, BRI1, CO2 assimilation, COR, SERK, brassinosteroid analogues, chlorophyll a fluorescence, frost tolerance, leaf reflectance,
• MeSH
• aklimatizace * MeSH
• Brassica napus * fyziologie   metabolismus   MeSH
• brassinosteroidy * metabolismus   MeSH
• listy rostlin metabolismus   fyziologie   MeSH
• nízká teplota * MeSH
• regulace genové exprese u rostlin * MeSH
• roční období MeSH
• rostlinné proteiny metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• brassinosteroidy * MeSH
• rostlinné proteiny MeSH

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.

• Klíčová slova
• BRI1 receptor kinase, Brassinosteroids, Cross-metathesis, Molecular docking, Organic synthesis, Plant bioassays,
• MeSH
• alkeny chemie   MeSH
• Arabidopsis účinky léků   enzymologie   růst a vývoj   MeSH
• brassinosteroidy chemická syntéza   chemie   metabolismus   farmakologie   MeSH
• hrách setý účinky léků   růst a vývoj   MeSH
• katalytická doména MeSH
• proteinkinasy chemie   metabolismus   MeSH
• proteiny huseníčku chemie   metabolismus   MeSH
• simulace molekulového dockingu MeSH
• techniky syntetické chemie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alkeny MeSH
• brassinosteroidy MeSH
• BRI1 protein, Arabidopsis MeSH Prohlížeč
• proteinkinasy MeSH
• proteiny huseníčku MeSH

Three types of brassinosteroid analogues with perfluoroalkylated side chains were synthesized by using alkene cross-metathesis of a brassinosteroid derivative bearing a terminal alkene moiety with different (perfluoroalkyl)propenes. The presence of the double bonds in the cross-metathesis products allowed a facile one-step double dihydroxylation to provide intermediates that after Baeyer-Villiger oxidation afforded the target compounds. Biological activity of the prepared analogues was tested in GABA(A) receptor, cytotoxic, and brassinolide activity, which reached in some cases the same range as their nonfluorinated analogues.

• MeSH
• alkeny chemie   MeSH
• biotest MeSH
• brassinosteroidy MeSH
• cholestanoly farmakologie   MeSH
• halogenace * MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• objevování léků MeSH
• potkani Wistar MeSH
• protinádorové látky chemická syntéza   chemie   metabolismus   farmakologie   MeSH
• receptory GABA-A metabolismus   MeSH
• steroidy heterocyklické farmakologie   MeSH
• steroidy chemická syntéza   chemie   metabolismus   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alkeny MeSH
• brassinolide MeSH Prohlížeč
• brassinosteroidy MeSH
• cholestanoly MeSH
• protinádorové látky MeSH
• receptory GABA-A MeSH
• steroidy heterocyklické MeSH
• steroidy MeSH

Antiangiogenic activity of the brassinosteroid plant hormones (BRs) and their derivative cholestanon was investigated in human umbilical vein endothelial cells (HUVEC) and in human microvascular endothelial cells (HMEC-1). 24-Epibrassinolide and 28-homocastasterone from group of 21 tested natural BRs inhibited migration of HUVEC cells. Seven tested BRs decreased the number of tubes significantly. Synthetic analogue cholestanon inhibited angiogenesis in vitro more effectively than natural BRs. Because of the similarity of BRs to human steroids, we have also studied interactions of BRs with human steroid receptors. Synthetic BRs cholestanon showed agonistic effects on estrogen-receptor-α, estrogen-receptor-β and androgen receptor. Of the natural BRs, 24-epibrassinolide was found to be a weak antagonist of estrogen-receptor-α (ERα). Our results provide the first evidence that large group of BRs can inhibit in vitro angiogenesis of primary endothelial cells. BRs constitute a novel group of human steroid receptor activators or inhibitors with capacity to inhibit angiogenesis.

• MeSH
• alfa receptor estrogenů metabolismus   MeSH
• beta receptor estrogenů metabolismus   MeSH
• brassinosteroidy metabolismus   farmakologie   MeSH
• endoteliální buňky pupečníkové žíly (lidské) účinky léků   metabolismus   MeSH
• fyziologická neovaskularizace účinky léků   MeSH
• inhibitory angiogeneze metabolismus   farmakologie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alfa receptor estrogenů MeSH
• beta receptor estrogenů MeSH
• brassinosteroidy MeSH
• inhibitory angiogeneze MeSH