Autor: Urban, M.; Soural, M.; Krajcovicova, S.; Hodon, J.; Stankova, J.; Dzubak, P.; Sarek, J.
Název práce v češtině: Cytotoxické Triterpeny – Syntéza a Mechanizmus Účinku
Název práce v angličtině: Cytotoxic Triterpenoids – Synthesis and Mechanism of action
Klíčová slova v češtině: triterpeny, cytotoxicita, mechanizmus účinku
Klíčová slova v angličtině:triterpenes, cytotoxicity, mechanism of action
Abstrakt česky: Byly připraveny série derivátů triterpenů a z nich vybráno několik zajímavých molekul. Z nich byly připraveny konjugáty s biotinem a BODIPY a ty byly využity pro stidium mechanizmu účinku.
Abstrakt anglicky: Triterpenoids are natural compounds that may be found in numerous living organisms, especially in plants. They often have interesting biological activities. Betulinic acid, for example, has strong anti-cancer activity and its hemiesters inhibit maturation of HIV particles.
In this work, a number of new derivatives of many terpenoid scaffolds (such as lupane, oleanane, ursane, taraxastane) was synthesized and tested on eight cancer and two non-cancer fibroblast lines. Compounds with cytotoxicity lower than 5 μM on cancer cell lines and non-toxic on fibroblasts were then selected for investigation of the mechanism of action. Most successful were heterocycles and highly oxidized structures. Solid-phase synthesis of conjugates of active compounds with a fluorescent tag was developed and using fluorescent microscopy, we were able to visualize their cellular uptake and distribution. Using analogous conjugates of terpenes with biotin (Figure 1) in pull-down assays, we isolated proteins that bind selectively to active terpenes and which are potential therapeutic targets. Synthetic aspects of the preparation of triterpenic conjugates as well as basic assumptions about mechanism of action and potential target proteins will be presented and discussed.
Jazyk v originále: Anglický
Publikace abstraktu: Sborník XX
Forma prezentace: zvaná přednáška
Název konference: 70. Sjezd Chemiků
Místo konání: Zlín (Czech Republic)
Datum konání: September 9 – 12
Rok konání: 2018
Způsob financování: IGA_PrF_2018_029, IGA_LF_2018_032