15 research outputs found
ΠΠ»ΠΈΡΠ½ΠΈΠ΅ ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ ΡΠΈΡΠΏΠ»Π°ΡΠΈΠ½Π° Ρ Π±ΡΠ°ΡΡΠΈΠ½ΠΎΡΡΠ΅ΡΠΎΠΈΠ΄Π°ΠΌΠΈ Π½Π° ΡΠΎΡΡ ΡΠ°ΠΊΠΎΠ²ΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ
In this work, the eο¬ect of brassinosteroids on the antitumor activity of classical cytostatic cisplatin in tumor cell lines A549 (human lung carcinoma) and Hep G2 (human hepatocellular carcinoma) was evaluated. Natural brassinosteroids 24-epibrassinolide and 28-homocastasterone, as well as their synthetic analogues (22S,23S)-24-epibrassinolide and (22S,23S)-28-homocastasterone were used. All four compounds with cisplatin inhibited the growth of cancer cells more eο¬ectively than cisplatin alone. Combinations with low concentrations of synthetic brassinosteroids were more eο¬ecient, and at 1 Β΅M decreased the IC50 of cisplatin by almost 2 times. The results suggest a possible benefit of combinations of classical antitumor drugs with brassinosteroids in overcoming the negative eο¬ects of chemotherapy by reducing their eο¬ective doses.ΠΠ·ΡΡΠ΅Π½ΠΎ Π²Π»ΠΈΡΠ½ΠΈΠ΅ ΠΏΡΠΈΡΠΎΠ΄Π½ΡΡ
Π±ΡΠ°ΡΡΠΈΠ½ΠΎΡΡΠ΅ΡΠΎΠΈΠ΄ΠΎΠ² 24-ΡΠΏΠΈΠ±ΡΠ°ΡΡΠΈΠ½ΠΎΠ»ΠΈΠ΄Π° ΠΈ 28-Π³ΠΎΠΌΠΎΠΊΠ°ΡΡΠ°ΡΡΠ΅ΡΠΎΠ½Π°, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΈΡ
ΡΠΈΠ½ΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π°Π½Π°Π»ΠΎΠ³ΠΎΠ² (22S,23S)-24-ΡΠΏΠΈΠ±ΡΠ°ΡΡΠΈΠ½ΠΎΠ»ΠΈΠ΄Π° ΠΈ (22S,23S)-28-Π³ΠΎΠΌΠΎΠΊΠ°ΡΡΠ°ΡΡΠ΅ΡΠΎΠ½Π° Π½Π° ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΊΠ»Π°ΡΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠΈΡΠΎΡΡΠ°ΡΠΈΠΊΠ° ΡΠΈΡΠΏΠ»Π°ΡΠΈΠ½Π° Π½Π° ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
Π»ΠΈΠ½ΠΈΡΡ
A549 (ΠΊΠ°ΡΡΠΈΠ½ΠΎΠΌΠ° Π»Π΅Π³ΠΊΠΈΡ
ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°) ΠΈ Hep G2 (ΠΊΠ°ΡΡΠΈΠ½ΠΎΠΌΠ° ΠΏΠ΅ΡΠ΅Π½ΠΈ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°). ΠΡΠ΅ ΡΠ΅ΡΡΡΠ΅ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ Π² ΡΠΎΡΠ΅ΡΠ°Π½ΠΈΠΈ Ρ ΡΠΈΡΠΏΠ»Π°ΡΠΈΠ½ΠΎΠΌ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π»ΠΈ ΡΠΎΡΡ ΡΠ°ΠΊΠΎΠ²ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ. ΠΠΎΠ»Π΅Π΅ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠΌΠΈ Π±ΡΠ»ΠΈ ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ Ρ Π½ΠΈΠ·ΠΊΠΈΠΌΠΈ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡΠΌΠΈ ΡΠΈΠ½ΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π±ΡΠ°ΡΡΠΈΠ½ΠΎΡΡΠ΅ΡΠΎΠΈΠ΄ΠΎΠ². ΠΡΠΈ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ Π±ΡΠ°ΡΡΠΈΠ½ΠΎΡΡΠ΅ΡΠΎΠΈΠ΄ΠΎΠ² Π² 1 ΠΌΠΊΠ IC50 ΡΠΈΡΠΏΠ»Π°ΡΠΈΠ½Π° ΡΠΌΠ΅Π½ΡΡΠ°Π»Π°ΡΡ ΠΏΠΎΡΡΠΈ Π² 2 ΡΠ°Π·Π°. ΠΠΎΠ»ΡΡΠ΅Π½Π½ΡΠ΅ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΡΡ ΠΎ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠΈ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΡ
Π΄ΠΎΠ· ΠΊΠ»Π°ΡΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² ΠΏΡΡΠ΅ΠΌ ΠΈΡ
ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΡ Π² ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ Ρ Π±ΡΠ°ΡΡΠΈΠ½ΠΎΡΡΠ΅ΡΠΎΠΈΠ΄Π°ΠΌΠΈ, ΡΡΠΎ ΡΠΏΠΎΡΠΎΠ±ΡΡΠ²ΠΎΠ²Π°Π»ΠΎ Π±Ρ ΡΠΌΡΠ³ΡΠ΅Π½ΠΈΡ Π½Π΅Π³Π°ΡΠΈΠ²Π½ΡΡ
ΠΏΠΎΡΠ»Π΅Π΄ΡΡΠ²ΠΈΠΉ Ρ
ΠΈΠΌΠΈΠΎΡΠ΅ΡΠ°ΠΏΠΈΠΈ
ΠΠΠ’ΠΠΠΠΠ¦ΠΠ ΠΠΠΠΠΠΠ― ΠΠΠ’ΠΠΠΠΠ‘Π’Π¬ ΠΠ ΠΠ‘Π‘ΠΠΠΠ‘Π’ΠΠ ΠΠΠΠΠ Π ΠΠΠ£Π₯ΠΠΠΠΠ«Π₯ ΠΠΠΠ’ΠΠΠ₯ ΠΠΠ Π¦ΠΠΠΠΠ« ΠΠΠ§ΠΠΠ
In this study, we first characterized the effect of natural brassinosteroids, 24-epibrassinolide (EBl) and 28-homocastasterone (HCS), and synthetic analogs, (22S,23S)-24-epibrassinolide and (22S,23S)-28-homocastastone, on the growth of the cancer cell line Hep G2 (hepatocellular carcinoma), as well as on the catalytic activity of cytochrome P450, which participates in the metabolism of most procarcinogens. All four compounds at high concentrations suppressed the proliferation of the test cell line. It is also interesting that at low concentrations, 24-EBl, (22S,23S)-24-EBl and (22S,23S)28-HCS activated significantly the Hep G2 cell growth. All studied brassinosteroids, except for 28-HCS, inhibited the activity of CYP1A1 and CYP1B1. The effect depended on the structure of the side chain and was more pronounced in the case of the SS orientation of the hydroxyl groups at the positions C22 and C23 ((22S,23S)-28-homocastasterone). The results of this work suggest that the studied brassinosteroids (especially (22S,23S)-28-homocastasterone) can be used to create effective drugs for tumor prevention and treatment.ΠΠΏΠ΅ΡΠ²ΡΠ΅ ΠΎΡ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΠΎΠ²Π°Π½ΠΎ Π²Π»ΠΈΡΠ½ΠΈΠ΅ ΠΏΡΠΈΡΠΎΠ΄Π½ΡΡ
Π±ΡΠ°ΡΡΠΈΠ½ΠΎΡΡΠ΅ΡΠΎΠΈΠ΄ΠΎΠ² 24-ΡΠΏΠΈΠ±ΡΠ°ΡΡΠΈΠ½ΠΎΠ»ΠΈΠ΄Π° (24-ΠΠ) ΠΈ 28-Π³ΠΎΠΌΠΎΠΊΠ°ΡΡΠ°ΡΡΠ΅ΡΠΎΠ½Π° (28-ΠΠΠ‘), Π° ΡΠ°ΠΊΠΆΠ΅ ΡΠΈΠ½ΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π°Π½Π°Π»ΠΎΠ³ΠΎΠ² (22S,23S)-24-ΡΠΏΠΈΠ±ΡΠ°ΡΡΠΈΠ½ΠΎΠ»ΠΈΠ΄Π° ΠΈ (22S,23S)-28-Π³ΠΎΠΌΠΎΠΊΠ°ΡΡΠ°ΡΡΠ΅ΡΠΎΠ½Π° Π½Π° ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π² ΡΠ°ΠΊΠΎΠ²ΠΎΠΉ ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ Π»ΠΈΠ½ΠΈΠΈ Hep G2 (ΠΊΠ°ΡΡΠΈΠ½ΠΎΠΌΠ° ΠΏΠ΅ΡΠ΅Π½ΠΈ), Π° ΡΠ°ΠΊΠΆΠ΅ Π½Π° ΠΊΠ°ΡΠ°Π»ΠΈΡΠΈΡΠ΅ΡΠΊΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΡΠΈΡΠΎΡ
ΡΠΎΠΌΠ° P450, ΠΊΠΎΡΠΎΡΡΠΉ ΡΡΠ°ΡΡΠ²ΡΠ΅Ρ Π² ΠΌΠ΅ΡΠ°Π±ΠΎΠ»ΠΈΠ·ΠΌΠ΅ Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²Π° ΠΏΡΠΎΠΊΠ°Π½ΡΠ΅ΡΠΎΠ³Π΅Π½ΠΎΠ². ΠΡΠ΅ ΡΠ΅ΡΡΡΠ΅ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΏΡΠΈ Π²ΡΡΠΎΠΊΠΈΡ
ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡΡ
Π±ΡΠ»ΠΈ Π°ΠΊΡΠΈΠ²Π½ΡΠΌΠΈ Π² ΠΏΠΎΠ΄Π°Π²Π»Π΅Π½ΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠΈ ΠΈΡΡΠ»Π΅Π΄ΡΠ΅ΠΌΠΎΠΉ Π»ΠΈΠ½ΠΈΠΈ. ΠΠ½ΡΠ΅ΡΠ΅ΡΠ½ΡΠΌ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΈ ΡΠΎΡ ΡΠ°ΠΊΡ, ΡΡΠΎ ΠΏΡΠΈ Π½ΠΈΠ·ΠΊΠΈΡ
ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡΡ
24-ΠΠ, (22S,23S)-24-ΠΠ ΠΈ (22S,23S)-28-ΠΠΠ‘ Π΄ΠΎΡΡΠΎΠ²Π΅ΡΠ½ΠΎ Π°ΠΊΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π»ΠΈ ΡΠΎΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ Hep G2. ΠΡΠ΅ ΠΈΡΡΠ»Π΅Π΄ΡΠ΅ΠΌΡΠ΅ Π±ΡΠ°ΡΡΠΈΠ½ΠΎΡΡΠ΅ΡΠΎΠΈΠ΄Ρ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π»ΠΈ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ CYP1A1 ΠΈ CYP1B1, Π·Π° ΠΈΡΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅ΠΌ 28-ΠΠΠ‘. ΠΠΊΠ°Π·ΡΠ²Π°Π΅ΠΌΡΠΉ ΡΡΡΠ΅ΠΊΡ Π·Π°Π²ΠΈΡΠ΅Π» ΠΎΡ ΡΡΡΡΠΊΡΡΡΡ Π±ΠΎΠΊΠΎΠ²ΠΎΠΉ ΡΠ΅ΠΏΠΈ ΠΈ Π±ΡΠ» Π±ΠΎΠ»Π΅Π΅ Π²ΡΡΠ°ΠΆΠ΅Π½ Π² ΡΠ»ΡΡΠ°Π΅ SSΠΎΡΠΈΠ΅Π½ΡΠ°ΡΠΈΠΈ Π³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ»ΡΠ½ΡΡ
Π³ΡΡΠΏΠΏ Π² ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΠΈ C22 ΠΈ Π‘23 ((22S,23S)-28-Π³ΠΎΠΌΠΎΠΊΠ°ΡΡΠ°ΡΡΠ΅ΡΠΎΠ½). ΠΠΎΠ»ΡΡΠ΅Π½Π½ΡΠ΅ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ ΡΠΊΠ°Π·ΡΠ²Π°ΡΡ Π½Π° Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΡ ΠΈΡΡΠ»Π΅Π΄ΡΠ΅ΠΌΡΡ
Π±ΡΠ°ΡΡΠΈΠ½ΠΎΡΡΠ΅ΡΠΎΠΈΠ΄ΠΎΠ² (Π² Π½Π°ΠΈΠ±ΠΎΠ»ΡΡΠ΅ΠΉ ΡΡΠ΅ΠΏΠ΅Π½ΠΈ (22S,23S)-28-ΠΠΠ‘) Π΄Π»Ρ ΡΠΎΠ·Π΄Π°Π½ΠΈΡ Π±ΠΎΠ»Π΅Π΅ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² Π΄Π»Ρ ΠΏΡΠΎΡΠΈΠ»Π°ΠΊΡΠΈΠΊΠΈ ΠΈ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ.
Relative and Absolute Configuration of Allohedycaryol. Enantiospecific Total Synthesis of Its Enantiomer
The enantiomer of (+)-allohedycaryol, a germacrane alcohol isolated from giant fennel (Ferula communis L.), has been synthesized, thereby elucidating the relative and absolute stereochemistry of the natural product. The synthesis of (-)-allohedycaryol started from (+)-Ξ±-cyperone (5) which was available in relatively large quantities via alkylation of imine 7 derived from (+)-dihydrocarvone and (R)-(+)-1-phenylethylamine. In a number of steps 5 was converted into the mesylate 4 with a regio- and stereoselective epoxidation as the key step. A Marshall fragmentation of 4 was used to prepare the trans,trans-cyclodeca-1,6-diene ring present in allohedycaryol. The conformation of synthetic (-)-allohedycaryol was elucidated via photochemical conversion into a bourbonane system. The synthesis of (-)-allohedycaryol also showed that natural (+)-allohedycaryol has the opposite absolute stereochemistry to that normally found in higher plants.
Synthesis of [7,7-2H2]epibrassinolide
Synthesis of labelled epibrassinolide containing two deuterium atoms in a position which is not subjected to isotopic exchange is reported. Key transformations include preparation of 6,7-seco steroidal diacid, its cyclization to a cyclic anhydride followed by a regioselective reduction with NaBD4. The obtained [7,7-2H2]epibrassinolide can be used in biochemical experiments when the loss of isotopic label should be avoide
Visible Light-Promoted Catalytic Ring-Opening Isomerization of 1,2-Disubstituted Cyclopropanols to Linear Ketones
In this article, we report a photocatalytic protocol for the isomerization of 1,2-disubstituted cyclopropanols to linear ketones. The reaction proceeds via radical intermediates and tolerates various functional groups
Palladium-Catalyzed 2-(Neopentylsulfinyl)aniline Directed C-H Acetoxylation and Alkenylation of the Arylacetamides
A directing group that promotes very fast diacetoxylation of the arylacetamides is reported. The auxiliary also promotes alkenylation with vinyl ketones, which were generated in one-pot from the cyclopropanols
Synthesis of ergostane-type brassinosteroids with modifications in ring A
Herein, we present a new strategy for the preparation of a broad range of brassinosteroid biosynthetic precursors/metabolites differing by the ring A fragment. The protocol is based on the use of readily available phytohormones of this class bearing a 2Ξ±,3Ξ±-diol moiety (epibrassinolide or epicastasterone) as starting materials. The required functionalities (Ξ2-, 2Ξ±,3Ξ±- and 2Ξ²,3Ξ²-epoxy-, 2Ξ±,3Ξ²-, 2Ξ²,3Ξ±-, and 2Ξ²,3Ξ²-dihydroxy-, 3-keto-, 3Ξ±- and 3Ξ²-hydroxy-, 2Ξ±-hydroxy-3-keto-) were synthesized from 2Ξ±,3Ξ±-diols in a few simple steps (CoreyβWinter reaction, epoxidation, oxidation, hydride reduction, etc.)
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 (Hordeum vulgare L.) plants to drought and to alter their endogenous brassinosteroid status. Germinated barley seeds were treated with 0.1 nM HBL or HCS solutions for two hours. A water deficit was created by stopping the watering of 7-day-old plants for the next two weeks. Plants responded to drought through growth inhibition, impaired water status, increased lipid peroxidation, differential effects on antioxidant enzymes, intense proline accumulation, altered expression of genes involved in metabolism, and decreased endogenous contents of hormones (28-homobrassinolide, B-ketones, and B-lactones). Pretreatment of plants with HBL reduced the inhibitory effect of drought on fresh and dry biomass accumulation and relative water content, whereas HCS partially reversed the negative effect of drought on fresh biomass accumulation, reduced the intensity of lipid peroxidation, and increased the osmotic potential. Compared with drought stress alone, pretreatment of plants with HCS or HBL followed by drought increased superoxide dismutase activity sevenfold or threefold and catalase activity (by 36%). The short-term action of HBL and HCS in subsequent drought conditions partially restored the endogenous B-ketone and B-lactone contents. Thus, the steroidal phytohormones HBL and HCS increased barley plant resistance to subsequent drought, showing some specificity of action
New synthesis of castasterone
An improved synthesis that could produce gram quantities of castasterone was proposed. The starting material was stigmasterol, the cyclic part of which was transformed in the first synthetic step into the 3Ξ±,5-cyclo-6-ketone. The side-chain carbon skeleton in the target compound was constructed with the required stereochemistry of the C-24 methyl via addition of methylacetylene, hydrogenation of the propargyl alcohol over Lindlar catalyst, and Claisen rearrangement. Diols were introduced using Sharpless asymmetric dihydroxylation of the intermediate β2,22-dienone in the presence of (DHQD)2AQN. A unique feature of the synthesis was the avoidance of chromatographic separations of propargyl alcohols with similar chromatographic mobilities because the C-22 diastereomers were enriched in subsequent redox reactions
New synthesis of castasterone
An improved synthesis that could produce gram quantities of castasterone was proposed. The starting material was stigmasterol, the cyclic part of which was transformed in the first synthetic step into the 3Ξ±,5-cyclo-6-ketone. The side-chain carbon skeleton in the target compound was constructed with the required stereochemistry of the C-24 methyl via addition of methylacetylene, hydrogenation of the propargyl alcohol over Lindlar catalyst, and Claisen rearrangement. Diols were introduced using Sharpless asymmetric dihydroxylation of the intermediate β2,22-dienone in the presence of (DHQD)2AQN. A unique feature of the synthesis was the avoidance of chromatographic separations of propargyl alcohols with similar chromatographic mobilities because the C-22 diastereomers were enriched in subsequent redox reactions