115032-59-2Relevant academic research and scientific papers
Substituted dienes prepared from betulinic acid – Synthesis, cytotoxicity, mechanism of action, and pharmacological parameters
Frydrych, Ivo,Urban, Milan,?arek, Jan,Benická, Sandra,D?ubák, Petr,Gurská, Soňa,Hajdúch, Marián,Kotulová, Jana,Li?ková, Barbora,Olejníková, Denisa,Pokorny, Jan
, (2021/07/28)
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.
Untersuchungen im Wittig-System nach einem ordnenden Konzept auf der Basis alternativer Prinzipien
Bandmann, Heinz,Bartik, Tamas,Bauckloh, Sylvia,Behler, Ansgar,Brille, Frank,et al.
, p. 193 - 204 (2007/10/02)
Our results show that the stereoselectivity of the Wittig-reaction can be controlled by the variation of substituents in accord with the ORDERING CONCEPT OF ALTERNATIV PRINCIPLES (individual pairs, known and unknown classes of alternatives).The "all-phenyl Wittig-system" having three phenyl groups on phosphorous two in ylid- and aldehyd-position was chosen as a standard for our investigations.Differentiation in ylid-position and compensation on phosphorous and aldehyd-position were observed by the comparison of "patterns".Consequently, most of the selectivity rules of Wittig-reactions can be explained by the differentiation through alternatives in the ylid-position.Inversion or conservation of the "patterns" of measured data points to the variation in structure of starting materials, reaction rates and selectivities.Amount-controls were also described in certain systems.
