The synthesis and anticancer activity of 2-styrylquinoline derivatives. A p53 independent mechanism of action
- Eur J Med Chem. 2019 Sep 1:177:338-349. doi: 10.1016/j.ejmech.2019.05.061.
- 1. 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 protected].
- 2. Institute of Chemistry, University of Silesia, 75 Pułku Piechoty 1a, 41-500, Chorzów, Poland.
- 3. A. Chełkowski Institute of Physics and Silesian Center for Education and Interdisciplinary Research, University of Silesia, 75 Pułku Piechoty 1a, 41-500, Chorzów, Poland.
- 4. Institute of Chemistry, University of Silesia, 75 Pułku Piechoty 1a, 41-500, Chorzów, Poland. Electronic address: [email protected].
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.