- Substituted dienes prepared from betulinic acid – Synthesis, cytotoxicity, mechanism of action, and pharmacological parameters
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A set of new substituted dienes were synthesized from betulinic acid by its oxidation to 30-oxobetulinic acid followed by the Wittig reaction. Cytotoxicity of all compounds was tested in vitro in eight cancer cell lines and two noncancer fibroblasts. Almost all dienes were more cytotoxic than betulinic acid. Compounds 4.22, 4.30, 4.33, 4.39 had IC50 below 5 μmol/L; 4.22 and 4.39 were selected for studies of the mechanism of action. Cell cycle analysis revealed an increase in the number of apoptotic cells at 5 × IC50 concentration, where activation of irreversible changes leading to cell death can be expected. Both 4.22 and 4.39 led to the accumulation of cells in the G0/G1 phase with partial inhibition of DNA/RNA synthesis at 1 × IC50 and almost complete inhibition at 5 × IC50. Interestingly, compound 4.39 at 5 × IC50 caused the accumulation of cells in the S phase. Higher concentrations of tested drugs probably inhibit more off-targets than lower concentrations. Mechanisms disrupting cellular metabolism can induce the accumulation of cells in the S phase. Both compounds 4.22 and 4.39 trigger selective apoptosis in cancer cells via intrinsic pathway, which we have demonstrated by changes in the expression of the crucial apoptosis-related protein. Pharmacological parameters of derivative 4.22 were superior to 4.39, therefore 4.22 was the finally selected candidate for the development of anticancer drug.
- Frydrych, Ivo,Urban, Milan,?arek, Jan,Benická, Sandra,D?ubák, Petr,Gurská, Soňa,Hajdúch, Marián,Kotulová, Jana,Li?ková, Barbora,Olejníková, Denisa,Pokorny, Jan
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- Non-competitive and selective dipeptidyl peptidase IV inhibitors with phenethylphenylphthalimide skeleton derived from thalidomide-related α-glucosidase inhibitors and liver X receptor antagonists
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Novel dipeptidyl peptidase IV (DPP-IV) inhibitors with a phenethylphenylphthalimide skeleton were prepared based on α-glucosidase inhibitors and liver X receptor (LXR) antagonists derived from thalidomide. Representative compounds showed non-competitive i
- Motoshima, Kazunori,Sugita, Kazuyuki,Hashimoto, Yuichi,Ishikawa, Minoru
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supporting information; experimental part
p. 3041 - 3045
(2011/06/24)
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- CH-Anion versus anion-π interactions in the crystal and in solution of pentafluorobenzyl phosphonium salts
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A series of phosphonium salts with pentafluorobenzyl substituents have been synthesized and were investigated in the crystal as well as in solution. The solid state structures of 1a, 1b and 2d reveal the presence of anion-π as well as CH-anion interactions. The two attractive, yet competitive forces seem to act in concert and a directing effect of the CH interaction on the relative position between anion and π-system is observed. The search for anion-π interactions in solution failed. Only CH-anion interactions proved to be important in solution.
- Mueller, Michael,Albrecht, Markus,Sackmann, Johannes,Hoffmann, Andreas,Dierkes, Fiete,Valkonen, Arto,Rissanen, Kari
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experimental part
p. 11329 - 11334
(2011/02/17)
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- Synthesis and spectroscopic and NLO properties of "push-pull" structures incorporating the inductive electron-withdrawing pentafluorophenyl group
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A series of "push-pull" molecules, each incorporating a pentafluorophenyl ring as an inductive accepting group, has been synthesised. The NLO properties of these compounds were measured in solution by EFISH (operating at 1907 nm) and in the solid state by
- Papagni, Antonio,Maiorana, Stefano,Del Buttero, Paola,Perdicchia, Dario,Cariati, Franco,Cariati, Elena,Marcolli, Walter
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p. 1380 - 1384
(2007/10/03)
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- Phenyl-perfluorophenyl stacking interactions: Topochemical [2+2] photodimerization and photopolymerization of olefinic compounds
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The face-to-face stacking interaction between phenyl and perfluorophenyl groups is emerging as a common noncovalent interaction. To explore the generality of this supramolecular synthon, the solid-state packing structure and reactivity of several monoolefins and diolefins substituted with phenyl and perfluorophenyl groups was investigated. Of the seven crystalline or cocrystalline materials investigated, six were found to undergo a photochemically induced [2+2] reaction in the solid state. By determining the stereochemistry of the photoproduct and/or X-ray structural analysis of the olefinic precursors, the stacked interaction between phenyl and perfluorophenyl groups in the photoactive crystals were revealed.
- Coates, Geoffrey W.,Dunn, Alex R.,Henling, Lawrence M.,Ziller, Joseph W.,Lobkovsky, Emil B.,Grubbs, Robert H.
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p. 3641 - 3649
(2007/10/03)
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- The Effect of Electron-Donating and Electron-Withdrawing Substituents on 1H- and 13C-NMR Chemical Shifts of Novel 7'-Aryl-Substituted 7'-Apo-β-carotenes
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The synthesis of 7'-aryl-7'-apo-β-carotenes, where aryl (Ar) is Ph, 4-NO2C6H4, 4-MeOC6H4, 4-(MeO2C)C6H4, C6F5, and 2,4,6-Me3C6H2, is described.NMR Chemical shifts of all H- and C-atoms are presented, together with specific examples of the spectra.In contrast to 1H chemical shifts which, except for H-C(8') and H-C(7'), did not differ greatly from those of β,β-carotene, considerable variations in 13C chemical shifts were observed.Signals of the C(α) atoms of the polyene chain nAr were shielded, those of the C(β) atoms were deshielded, with some exceptions when n = 1; the effects decreased with increasing n.
- Hand, Elli S.,Belmore, Kenneth A.,Kispert, Lowell D.
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p. 1928 - 1938
(2007/10/02)
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- Perfluoro-keto-ylids as precursors of polychloroketones, 1,2-diketones and quinoxalines
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The invention relates to a novel fluorinated pre-polymer and novel process steps in producing the same. The pre-polymers are quinoxaline materials derived by reaction of diketone linkage containing perfluoro-compounds with an aromatic diamine. The diketone is produced by a bis-ketone. The polychloroketone is produced by reacting a keto-ylid with a chlorinating agent, e.g., chlorine. The keto-ylid is produced by oxidatively dechlorinating a polychloroketone which may be a monoketone or reacting a phosphorane with an acid halide of a polyoxy-perfluoroalkylene oxide wherein the perfluoro-oxyalkylene group contains two or three carbon atoms, and there are present from two or twenty perfluoro-oxyalkylene units in the oligomer. The quinoxalines, the polychloroketones and the diketones hereof are novel products. Cross-linking may be effected with a free radical generator.
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- Perfluoro-keto-ylids as precursors of polychloroketones, 1,2-diketones and quinoxalines
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The invention relates to a novel fluorinated pre-polymer and novel process steps in producing the same. The pre-polymers are quinoxaline materials derived by reaction of diketone linkage containing perfluoro-compounds with an aromatic diamine. The diketone is produced by oxidatively dechlorinating a polychloroketone which may be a monoketone or a bis-ketone. The polychloroketone is produced by reacting a keto-ylid with a chlorinating agent, e.g., chlorine. The keto-ylid is produced by reacting a phosphorane with an acid halide of a polyoxy-perfluoroalkylene oxide wherein the perfluoro-oxyalkylene group contains two or three carbon atoms, and there are present from two to twenty perfluoro-oxyalkylene units in the oligomer. The quinoxalines, the polychloroketones and the diketones hereof are novel products. Cross-linking may be effected with a free radical generator.
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