Autor: Borková, L.; Gurská, S.; Lišková, B.; Hajdúch, M.; Šarek, J.; Drašar, P.; Urban M.
Název práce v češtině: Triterpeny modifikované na A-kruhu – syntéza a protinádorové vlastnosti
Název práce v angličtině: A-Ring Modified Triterpenes – Synthesis and Anticancer Properties
Klíčová slova v češtině: triterpeny, cytotoxicita, A-kruh
Klíčová slova v angličtině:triterpenes, cytotoxicity, A-ring
Abstrakt česky: Byly připraveny triterpeny modifikované na A-kruhu, např. thiazoly a také molekuly substituované v poloze 2 pomocí Suzukiho reakce. Tyto sloučeniny vykázaly zajímavou cytotoxicitu, vliv na buněčný cyklus a jsou nadějnými kandidáty na potenciální léčbu rakoviny.
Abstrakt anglicky: Modification of the A-ring of natural pentacyclic triterpenoids is one of the most popular synthetic trends in current development of new antitumor triterpenoids. 2,2-Difluorodihydrobetulinic acid and its derivatives belong to the most cytotoxic compounds prepared recently, however their toxicity on non-cancer fibroblasts was one of the major drawbacks. In order to find active derivatives with better selectivity, 70 triterpenoids modified by fused heterocycles (Fig. 1, e.g. 1) and 40 compounds with aromatic substituents placed to the C-2 or C-3 position via Suzuki-Miyaura cross-coupling (Fig. 1, e.g. 2 or 3) were synthesised in this work. A number of new compounds had IC50 < 5 μM with high selectivity against cancer cells. Influence of the best compounds on cell cycle and on the DNA/RNA synthesis was studied. Their pharmacological parameters were measured, such as chemical, plasma, and metabolic stability, membrane permeability, binding to plasma proteins. Based on the results, four derivatives were selected for future in vivo tests on murine tumor models. Synthesis, cytotoxicity, structure-activity relationships, and pharmacological parameters of this set of compounds will be shown and discussed.
Jazyk v originále: Anglický
Publikace abstraktu: Sborník str. 45/154
Forma prezentace: Přednáška
Název konference: 53rd. Advances in Organic, Bioorganic, and Pharmaceutical Chemistry, „Liblice 2018“
Místo konání: Lázně Bělohrad (Czech Republic)
Datum konání: November 2 – 4
Rok konání: 2018
Způsob financování: GAČR 15-05620S, IGA_PrF_2018_029, IGA_LF_2018_032