par Madonna, Sébastien;Béclin, Christophe;Laras, Younes;Moret, Vincent;Marcowycz, Aline ;Lamoral-Theys, Delphine ;Dubois, Jacques ;Barthelemy-Requin, Magali;Lenglet, Gaëlle;Depauw, Sabine;Cresteil, Thierry;Aubert, Geneviève;Monnier, Valérie;Kiss, Robert ;David-Cordonnier, Marie-Hélène;Kraus, Jean-Louis
Référence European journal of medicinal chemistry, 45, 2, page (623-638)
Publication Publié, 2010-02
Référence European journal of medicinal chemistry, 45, 2, page (623-638)
Publication Publié, 2010-02
Article révisé par les pairs
Résumé : | A series of twenty six 8-hydroxyquinoline substituted amines, structurally related to compounds 2 and 3, were synthesized to evaluate the effects of structural changes on antitumor activity and understand their mechanism of action. The studies were performed on a wide variety of cancer cell lines within glioma and carcinoma models. The results obtained from chemical models and biological techniques such as microarrays suggest the following hypothesis that a quinone methide intermediate which does not react with DNA but which gives covalent protein thiol adducts. Micro-array analysis showed that the drugs induce the expression of a variety of stress related genes responsible for the cytotoxic and cytostatic effects in carcinoma and glioblastoma cells respectively. The described analogues could represent new promising anti-cancer candidates with specific action mechanisms, targeting accessible thiols from specific proteins and inducing potent anti-cancer effects. |