title: Design, Synthesis and In Vitro Activity of Anticancer Styrylquinolines. The p53 Independent Mechanism of Action.
abstract: 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.
authors.affiliation: A. Chełkowski Institute of Physics, University of Silesia, Katowice, Poland.|Silesian Center for Education and Interdisciplinary Research, University of Silesia, Chorzów, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Mrozek-Wilczkiewicz
authors.affiliation: Institute of Chemistry, University of Silesia, Katowice, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Spaczynska
authors.affiliation: Institute of Chemistry, University of Silesia, Katowice, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Malarz
authors.affiliation: Institute of Chemistry, University of Silesia, Katowice, Poland.
authors.forename: Wioleta
authors.initials: W
authors.lastname: Cieslik
authors.affiliation: A. Chełkowski Institute of Physics, University of Silesia, Katowice, Poland.|Silesian Center for Education and Interdisciplinary Research, University of Silesia, Chorzów, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Rams-Baron
authors.affiliation: Laboratory of Growth Regulators, Centre of the Region Haná for Biotechnological and Agricultural Research, Palacký University and Institute of Experimental Botany AS CR, Olomouc, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Kryštof
authors.affiliation: Institute of Chemistry, University of Silesia, Katowice, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Musiol
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D017209:Apoptosis; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics*; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D004247:DNA / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000378:metabolism; D045325:HCT116 Cells / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis; D020128:Inhibitory Concentration 50; D007364:Intercalating Agents / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D009154:Mutation; D011804:Quinolines / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D014404:Tubulin / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D007364:Intercalating Agents; D011804:Quinolines; C495901:TP53 protein, human; D014404:Tubulin; D016159:Tumor Suppressor Protein p53; C481600:styrylquinoline; D004317:Doxorubicin; D004247:DNA; D020169:Caspases