Design, Synthesis and In Vitro Activity of Anticancer Styrylquinolines. The p53 Independent Mechanism of Action

0454119 - ÚEB 2016 RIV US eng J - Článek v odborném periodiku
Mrozek-Wilczkiewicz, A. - Spaczynska, E. - Malarz, K. - Cieslik, W. - Rams-Baron, M. - Kryštof, Vladimír - Musiol, R.
Design, Synthesis and In Vitro Activity of Anticancer Styrylquinolines. The p53 Independent Mechanism of Action.
PLoS ONE. Roč. 10, č. 11 (2015), e0142678. ISSN 1932-6203. E-ISSN 1932-6203
Grant CEP: GA MŠMT(CZ) LO1204
Institucionální podpora: RVO:61389030
Klíčová slova: BIOLOGICAL-ACTIVITY SPECTRUM * MUTANT P53 * QUINOLINE DERIVATIVES
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 3.057, rok: 2015

A group of styrylquinolines were synthesized and tested for their anti-proliferative activity. Anti-proliferative activity was evaluated against the human colon carcinoma cell lines that had a normal expression of the p53 protein (HCT116 p53(+/+)) and mutants with a disabled TP53 gene (HCT116 p53(-/-)) and against the GM 07492 normal human fibroblast cell line. A SAR study revealed the importance of Cl and OH as substituents in the styryl moiety. Several of the compounds that were tested were found to have a marked anti-proliferative activity that was similar to or better than doxorubicin and were more active against the p53 null than the wild type cells. The cellular localization tests and caspase activity assays suggest a mechanism of action through the mitochondrial pathway of apoptosis in a p53-independent manner. The activity of the styrylquinoline compounds may be associated with their DNA intercalating ability.
Trvalý link: http://hdl.handle.net/11104/0254975