title: Another step toward DNA selective targeting: Ni(II) and Cu(II) complexes of a Schiff base ligand able to bind gene promoter G-quadruplexes.
abstract: DNA G-rich sequences are able to form four-stranded structures organized in stacked guanine tetrads. These structures, called G-quadruplexes, were found to have an important role in the regulation of oncogenes expression and became, for such a reason, appealing targets for anticancer drugs. Aiming at finding selective G-quadruplex binders, we have designed, synthesized and characterized a new water soluble Salen-like Schiff base ligand and its Ni(II) and Cu(II) metal complexes. UV-Vis, circular dichroism and FRET measurements indicated that the nickel complex can stabilize oncogene promoter G-quadruplexes with high selectivity, presenting no interactions with duplex DNA at all. The same compound exhibited dose-dependent cytotoxic activity in MCF-7 breast cancer cells when combined with lipofectamine as lipophilic carrier.
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Waehringerstr. 42, A-1090 Vienna, Austria. alessio.terenzi@univie.ac.at and Research Platform "Translational Cancer Therapy Research", University of Vienna and Medical University of Vienna, Vienna, Austria.
authors.forename: Alessio
authors.initials: A
authors.lastname: Terenzi
authors.affiliation: Department of Medicine I, Institute of Cancer Research and Comprehensive Cancer Center, Medical University Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lötsch
authors.affiliation: Department of Medicine I, Institute of Cancer Research and Comprehensive Cancer Center, Medical University Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Sushilla
authors.initials: S
authors.lastname: van Schoonhoven
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Waehringerstr. 42, A-1090 Vienna, Austria. alessio.terenzi@univie.ac.at.
authors.forename: Alexander
authors.initials: A
authors.lastname: Roller
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Waehringerstr. 42, A-1090 Vienna, Austria. alessio.terenzi@univie.ac.at and Research Platform "Translational Cancer Therapy Research", University of Vienna and Medical University of Vienna, Vienna, Austria.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Kowol
authors.affiliation: Research Platform "Translational Cancer Therapy Research", University of Vienna and Medical University of Vienna, Vienna, Austria and Department of Medicine I, Institute of Cancer Research and Comprehensive Cancer Center, Medical University Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Berger
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Waehringerstr. 42, A-1090 Vienna, Austria. alessio.terenzi@univie.ac.at and Research Platform "Translational Cancer Therapy Research", University of Vienna and Medical University of Vienna, Vienna, Austria.
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Viale delle Scienze, Edificio 17, 90128 Palermo, Italy. giampaolo.barone@unipa.it.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Barone
mesh_terms: D002942:Circular Dichroism; D003300:Copper; D004247:DNA; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D006801:Humans; D008024:Ligands; D061986:MCF-7 Cells; D058990:Molecular Targeted Therapy; D009532:Nickel; D011401:Promoter Regions, Genetic; D012545:Schiff Bases
chemical_list: D008024:Ligands; D012545:Schiff Bases; D003300:Copper; D009532:Nickel; D004247:DNA