title: Toward the Development of Specific G-Quadruplex Binders: Synthesis, Biophysical, and Biological Studies of New Hydrazone Derivatives.
abstract: G-Quadruplex-binding compounds are currently perceived as possible anticancer therapeutics. Here, starting from a promising lead, a small series of novel hydrazone-based compounds were synthesized and evaluated as G-quadruplex binders. The in vitro G-quadruplex-binding properties of the synthesized compounds were investigated employing both human telomeric and oncogene promoter G-quadruplexes with different folding topologies as targets. The present investigation led to the identification of potent G-quadruplex stabilizers with high selectivity over duplex DNA and preference for one G-quadruplex topology over others. Among them, selected derivatives have been shown to trap G-quadruplex structures in the nucleus of cancer cells. Interestingly, this behavior correlates with efficient cytotoxic activity in human osteosarcoma and colon carcinoma cells.
authors.affiliation: Department of Pharmacy, University of Naples "Federico II" , via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Jussara
authors.initials: J
authors.lastname: Amato
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna , 40126 Bologna, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Morigi
authors.affiliation: Department of Pharmacy, University of Naples "Federico II" , via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pagano
authors.affiliation: Department of Pharmacy, University of Naples "Federico II" , via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Pagano
authors.affiliation: UCL School of Pharmacy, University College London , London WC1N 1AX, U.K.
authors.forename: Stephan
authors.initials: S
authors.lastname: Ohnmacht
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna , 40126 Bologna, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: De Magis
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna , 40126 Bologna, Italy.
authors.forename: Yee-Peng
authors.initials: YP
authors.lastname: Tiang
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna , 40126 Bologna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Capranico
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna , 40126 Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Locatelli
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna , 40126 Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Graziadio
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna , 40126 Bologna, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Leoni
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna , 40126 Bologna, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Rambaldi
authors.affiliation: Department of Pharmacy, University of Naples "Federico II" , via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.affiliation: UCL School of Pharmacy, University College London , London WC1N 1AX, U.K.
authors.forename: Stephen
authors.initials: S
authors.lastname: Neidle
authors.affiliation: Department of Pharmacy, University of Naples "Federico II" , via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Randazzo
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D054856:G-Quadruplexes / Q000187:drug effects*; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D006835:Hydrazones; D004247:DNA