title: Xanthene and xanthone derivatives as G-quadruplex stabilizing ligands.
abstract: Following previous studies on anthraquinone and acridine-based G-quadruplex ligands, here we present a study of similar aromatic cores, with the specific aim of increasing G-quadruplex binding and selectivity with respect to duplex DNA. Synthesized compounds include two and three-side chain xanthone and xanthene derivatives, as well as a dimeric "bridged" form. ESI and FRET measurements suggest that all the studied molecules are good G-quadruplex ligands, both at telomeres and on G-quadruplex forming sequences of oncogene promoters. The dimeric compound and the three-side chain xanthone derivative have been shown to represent the best compounds emerging from the different series of ligands presented here, having also high selectivity for G-quadruplex structures with respect to duplex DNA. Molecular modeling simulations are in broad agreement with the experimental data.
authors.affiliation: Dipartimento di Chimica, Università di Roma "La Sapienza", Piazzale Aldo Moro 5, Roma 00185, Italy. alessandro.altieri@uniroma1.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Altieri
authors.forename: Antonello
authors.initials: A
authors.lastname: Alvino
authors.forename: Stephan
authors.initials: S
authors.lastname: Ohnmacht
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Ortaggi
authors.forename: Stephen
authors.initials: S
authors.lastname: Neidle
authors.forename: Daniele
authors.initials: D
authors.lastname: Nocioni
authors.forename: Marco
authors.initials: M
authors.lastname: Franceschin
authors.forename: Armandodoriano
authors.initials: A
authors.lastname: Bianco
mesh_terms: D054856:G-Quadruplexes; D006801:Humans; D056004:Molecular Dynamics Simulation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D014966:Xanthenes / Q000737:chemistry*; D044004:Xanthones / Q000737:chemistry*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D014966:Xanthenes; D044004:Xanthones; C009689:xanthone