- 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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- Synthesis of aryl and heterocyclic polyenes and their activity in free radical scavenging
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Aryl polyenes and heterocyclic polyenes with the same central C20 unit of β,β-carotene but different terminal groups were synthesised. Their free radical scavenging activity was measured by a 1,1-diphenyl-2-picrylhydrazinyl spectrophotometric method. The results indicated that all the new compounds have free radical scavenging activity.
- Deng, Kaini,Yang, Zuxing,Luo, Juan,Wu, Kaiqun
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p. 129 - 132
(2018/04/20)
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- Kinetics of proton transfer from phosphonium ions to electrogenerated bases: Polar, steric and structural influences on kinetic acidity and basicity
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Derivative cyclic voltammetry (DCV) and linear sweep voltammetry (LSV) have been used to measure rates of proton transfer in DMSO solution between different types of electrogenerated base (EGB) and a series of phosphonium ions of relevance to ylide formation for synthetic reactions. Although the electrochemical methods are convenient for the measurement of rates of proton transfer in these systems a major conclusion of the study is that considerable care must be exercised in the application of the methods and in drawing general conclusions from the results. In particular, comparison of kinetic acidity with thermodynamic pK values in DMSO shows that a single Bronsted relationship does not hold for the series of phosphonium ions. The kinetic acidities are profoundly affected by: whether the EGB is a carbon or nitrogen base; the propensity of some of the phosphonium ions to enolise; and steric factors. Other measures of electron-demand at the acidic methylene groups (13C and 1H chemical shifts, reduction potentials) are consistent with the pK(DMSO) values. The kinetic results confirm that the Ph3P+ group is, for non-enolisable phosphonium salts, more activating than Bu3P+.
- Bettencourt, Ana-Paula,Freitas, Ana Maria,Montenegro, M. Irene,Nielsen, Merete Folmer,Utley, James H. P.
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p. 515 - 522
(2007/10/03)
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- A Facile and New Route for the Synthesis of Substituted 1,2-Dithiafulvenes Using Phosphonium Ylides
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A wide variety of 6-aryl-5-phenyl-1,2-dithiafulvenes and 6-aroyl-5-phenyl-1,2-dithiafulvenes (4) have been synthesized by the interaction of 5-phenyl-1,2-dithiol-3-one (3a) and phosphonium ylides (2).The synthesis of these dithiafulvenes has also been car
- Gupta, K. C.,Saxena, B. K.,Pathak, P. K.
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p. 312 - 314
(2007/10/02)
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- Reactions of Allylidenephosphoranes with Heterocumulenes,I. - Vinylketenimines
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According to their α-substituent the allylidenephosphoranes 4 are converted by isocyanates either via Wittig reaction into the hitherto little known vinylketenimines 7 or by carbamoylation and ring closure into the pyrrolone 5 or the 3-pyridylidenephospho
- Capuano, Lilly,Willmes, Arnold
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