Autor: Urban, M.; Borková, L.; Pokorný, J.; Džubák, P.; Hajdúch, M.; Soural, M.; Šarek, J.; Krajčovičová, S.; Řehulka, J.; Hodoň, J.
Název práce v češtině: Triterpeny s Protinádorovými Účinky, Jejich Syntéza a Mechanizmus Účinku
Název práce v angličtině: Triterpenes with Antitumor Properties, their Synthesis and Mechanism of Action
Klíčová slova v češtině: triterpeny, protinádorová aktivita, mechanizmus účinku
Klíčová slova v angličtině:triterpenes, antitumor activity, mechanism of action
Abstrakt česky: Bylo připraveno mnoho triterpenů a zkoumán jejich mechanizmus účinku. Nejlepší deriváty byly testovány in vivo na nádorových modelech.
Abstrakt anglicky: Triterpenoids are natural secondary metabolites that are commonly found in plants. They often have various biological activities. Betulinic acid is one of the most promising terpenes because it has strong anti-tumor activity and its derivatives inhibit maturation of HIV particles.
In this work, a set of more than 50 heterocyclic derivatives of various terpenoid skeletons (such as lupane, oleanane, ursane, taraxastane) was synthesized with a heterocycle moiety condensed to the A-ring of the molecule (Fig. 1). In addition, a set of 45 betulinic acid derivatives with an electronegative substituent at the position C-2 was prepared. All compounds were tested on eight cancer and two non-cancer fibroblast lines. Triterpenic pyrazines (e.g. compound 1), aminothiazoles, pyridines, and diosphenols (e.g. 2) had cytotoxicity lower than 5 μM on CCRF-CEM cell line and often on the other cancer cell lines and they were non-toxic on fibroblasts, having the selectivity index of 5-99. Influence of the best compounds on cell cycle and on the DNA/RNA synthesis was studied. In order to understand their mechanism of action, solid-phase synthesis of conjugates of active compounds with a fluorescent tag or biotin was developed to get conjugates such as molecule 3 and currently, we keep isolating the target proteins in pull down assays. Pharmacological parameters were measured for the 10 best derivatives prepared here and based on the results, two compounds were selected for in vivo tests on mice. One compound (analogue of 2) had significant antitumor activity. Basic assumptions about structure-activity relationships, possible pharmacophores, target proteins, and in vivo activity will be discussed.
Jazyk v originále: Anglický
Publikace abstraktu: Sborník 42/xxx
Forma prezentace: Přednáška
Název konference: International Symposium on “Natural Products in Cancer Prevention and Therapy,” Trends in Methods and Modelling
Místo konání: Napoli (Italy)
Datum konání: September 3 – 7
Rok konání: 2018
Způsob financování: N/A