title: Water soluble extended naphthalene diimides as pH fluorescent sensors and G-quadruplex ligands.
abstract: Extended naphthalene diimides (NDIs) fused to 1,4-dihydropyrazine-2,3-dione, containing two solubilizing moieties, have been synthesized. Fluorescence spectra of the new NDIs were remarkably affected by pH, as the second deprotonation of the dihydropyrazinedione moiety (pK(a) 6.9) switched off the emission. Binding to a G-quadruplex folded oligonucleotide and stoichiometry were evaluated by FRET melting assay and CD analysis. G-quadruplex binding was strongly enhanced shifting from pH 7.4 to pH 6.0 as a consequence of the dihydropyrazinedione moiety protonation. Cytotoxicity studies using two human telomerase-positive cell lines (HT29 and A549) revealed that the best G-quadruplex ligand was very active against the colon cell line, with an EC(50) of 300 nM.
authors.affiliation: Dipartimento di Chimica, Università di Pavia, Pavia, Italy. filippo.doria@unipv.it
authors.forename: Filippo
authors.initials: F
authors.lastname: Doria
authors.forename: Matteo
authors.initials: M
authors.lastname: Nadai
authors.forename: Giovanna
authors.initials: G
authors.lastname: Sattin
authors.forename: Luca
authors.initials: L
authors.lastname: Pasotti
authors.forename: Sara N
authors.initials: SN
authors.lastname: Richter
authors.forename: Mauro
authors.initials: M
authors.lastname: Freccero
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005456:Fluorescent Dyes / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007094:Imides / Q000737:chemistry*; D008024:Ligands; D009281:Naphthalenes / Q000737:chemistry* / Q000494:pharmacology; D010084:Oxidation-Reduction; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D005456:Fluorescent Dyes; D007094:Imides; D008024:Ligands; D009281:Naphthalenes; D014867:Water; C031721:naphthalene