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.

• MeSH
• Alkenes chemistry   MeSH
• Arabidopsis drug effects   enzymology   growth & development   MeSH
• Brassinosteroids chemical synthesis   chemistry   metabolism   pharmacology   MeSH
• Pisum sativum drug effects   growth & development   MeSH
• Catalytic Domain MeSH
• Protein Kinases chemistry   metabolism   MeSH
• Arabidopsis Proteins chemistry   metabolism   MeSH
• Molecular Docking Simulation MeSH
• Chemistry Techniques, Synthetic MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Chemistry MeSH

• Conspectus
• Organická chemie
• NML Fields
• chemie, klinická chemie
• NML Publication type
• učebnice vysokých škol

Despite intensive research efforts, the distinct biological roles of two closely related estrogen receptors, ERα and ERβ, are only partially understood. Therefore, ligands selective for either of two isotypes are useful research tools because they allow for exerting a desired subset of biological effects mediated by only one of the receptors. Here we report on the synthesis of a new class of potent and selective ligands for ERα represented by a series of 17α-substituted estradiols bearing lipophilic perfluoroalkyl chains. These 17α-perfluoroalkylated estradiols were synthesized by Ru-catalyzed cross metathesis reactions of 17α-allyl- or 17α-vinylestradiols with perfluoroalkylpropenes. Compounds were tested in both agonistic and antagonistic modes using a panel of stable steroid receptor reporter cell lines established in U2OS cells and consisting of ERα-LBD, ERβ-LBD, GR-LBD, and MR-LBD reporters. Some of the compounds are potent and selective agonists of ERα, exhibiting weak partial to no detectable agonistic activity on ERβ. Notably, 11c is the most ERα selective ligand of the prepared compounds because it activates ERα but inhibits ERβ. In addition, some compounds are pure agonists on ERα but show mixed agonistic/antagonistic profile on ERβ which is a typical pattern observed for selective estrogen receptor modulators (SERMs).

• MeSH
• Transcriptional Activation MeSH
• Estrogen Receptor alpha agonists   antagonists & inhibitors   MeSH
• Estrogen Receptor beta agonists   antagonists & inhibitors   MeSH
• Estradiol analogs & derivatives   chemical synthesis   pharmacology   MeSH
• Humans MeSH
• Ligands MeSH
• Cell Line, Tumor MeSH
• Selective Estrogen Receptor Modulators chemical synthesis   pharmacology   MeSH
• Stereoisomerism MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't 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
• Alkenes chemistry   MeSH
• Biological Assay MeSH
• Cholestanols pharmacology   MeSH
• Rats MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Drug Discovery MeSH
• Rats, Wistar MeSH
• Antineoplastic Agents pharmacology   chemical synthesis   chemistry   metabolism   MeSH
• Receptors, GABA-A metabolism   MeSH
• Steroids, Heterocyclic pharmacology   MeSH
• Steroids chemical synthesis   chemistry   metabolism   pharmacology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH