Autor: Borkova, L.; Sarek, J.; Rehulka, J.; Dzubak, P.; Hajduch, M.; Piskorova, K.; Urban, M.
Název práce v češtině: Cytotoxická aktivita triterpenů substituovaných v pozici 2
Název práce v angličtině: Cytotoxic Activity of Triterpenes Substituted in the Position 2
Klíčová slova v češtině: triterpeny, cytotoxicita, substituce
Klíčová slova v angličtině:triterpenes, cytotoxicity, substitution
Abstrakt česky: Byly syntetizovány triterpeny se substituenty v poloze 2 a změřena jejich cytotoxicity. Bylo zjištěno, že čím vyšší elektronegativita substituentu, tím vyšší cytotoxická aktivita a tím horší selektivita.
Abstrakt anglicky: The aim of this work was to synthesize a set of 2-substituted derivatives of lupane and 18α-oleanane, and to investigate their cytotoxic activities. There are several known derivatives of lupane with high cytotoxic activity and all of them contain an electronegative substituent at the position 2 of the lupane skeleton such as 1 or 2 (when R=OH).1 It seemed that their cytotoxicity is driven by the electronegativity of the substituent. In order to confirm or refute this theory, a small library of triterpenoids modified at C-2 was synthesized. First of all, a set of difluoroderivatives was prepared as examples of the ultimately electronegative substituents.2 Secondly; we introduced a number of other electron withdrawing groups (compound 2 where R=NH2, NO2, CN, SH, CH2NH2 etc.) to the parent molecule, mostly by nucleophilic substitution of bromoketone 1.
Cytotoxicity of all compounds was measured with best to be 2,2-difluorodihydrobetulonic acid (3) with IC50 = 2 μmol/L. Cell cycle analysis in CCRF-CEM cells proved G1/S phase block induced by compound 3. Most of other compounds had medium or high cytotoxicity; the higher was the electronegativity of the substituent, the lower was the IC50 which seems to support our theory. On the other hand, steric effects or possibility of enolization of the ketone at C-3 also may play an important role.
Jazyk v originále: Anglický
Publikace abstraktu: Sborník 59/166
Forma prezentace: poster
Název konference: Advances in Organic, Bioorganic and Pharmaceutical Chemistry „Liblice 2015“
Místo konání: Olomouc (Czech Republic)
Datum konání: November 6-8
Rok konání: 2015
Způsob financování: GACR Reg. No 15-05620S