title: Design and synthesis of a new dimeric xanthone derivative: enhancement of G-quadruplex selectivity and telomere damage.
abstract: Following the results we previously reported on a series of xanthene and xanthone derivatives as G-quadruplex stabilizing ligands, in order to obtain a more selective compound with respect to the previous generation of derivatives, we decided to modify the structure of the core ligand, specifically its aromatic extension. In particular, here we report the design, synthesis and activity data of a new compound obtained by dimerization of the xanthene core (HELIXA4C). The reported results show that extension of the aromatic core and the increase of the number of polar side chains led to a great enhancement of G-quadruplex selectivity and telomere damage capability, as derived using ESI-MS evaluation, in vitro cancer screening and specific immunofluorescence assays.
authors.affiliation: University of Rome "Sapienza", Department of Chemistry, Piazzale Aldo Moro 5, Roma 00185, Italy. alessandro.altieri@uniroma1.it marco.franceschin@uniroma1.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Franceschin
authors.forename: Daniele
authors.initials: D
authors.lastname: Nocioni
authors.forename: Annamaria
authors.initials: A
authors.lastname: Biroccio
authors.forename: Emanuela
authors.initials: E
authors.lastname: Micheli
authors.forename: Stefano
authors.initials: S
authors.lastname: Cacchione
authors.forename: Chiara
authors.initials: C
authors.lastname: Cingolani
authors.forename: Alessandro
authors.initials: A
authors.lastname: Venditti
authors.forename: Pasquale
authors.initials: P
authors.lastname: Zizza
authors.forename: Armandodoriano
authors.initials: A
authors.lastname: Bianco
authors.forename: Alessandro
authors.initials: A
authors.lastname: Altieri
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019281:Dimerization; D054856:G-Quadruplexes / Q000187:drug effects*; D006801:Humans; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D016615:Telomere / Q000187:drug effects*; D044004:Xanthones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D044004:Xanthones