The synthesis and anticancer activity of 2-styrylquinoline derivatives. A p53 independent mechanism of action.


A. Chełkowski Institute of Physics and Silesian Center for Education and Interdisciplinary Research, University of Silesia, 75 Pułku Piechoty 1a, 41-500, Chorzów, Poland. Electronic address: [Email]


A series of styrylquinolines was designed and synthesized based on the four main quinoline scaffolds including oxine, chloroxine and quinolines substituted with a hydroxyl group or chlorine atom at the C4 position. All of the compounds were tested for their anticancer activity on wild-type colon cancer cells (HCT 116) and those with a p53 deletion. Analysis of SAR revealed the importance of electron-withdrawing substituents in the styryl part and chelating properties in the quinoline ring. The compounds that were more active were also tested on a panel of four cancer cell lines with mutations in TP53 tumor suppressor gene. The results suggest that styrylquinolines induce cell cycle arrest and activate a p53-independent apoptosis. The apparent mechanism of action was studied for the most promising compounds, which produced reactive oxygen species and changed the cellular redox balance.


2-Styrylquinoline derivatives,Anticancer activity,Apoptosis,Cell cycle inhibition,Reactive oxygen species,p53 protein,

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