title: Synthesis, Binding Properties, and Differences in Cell Uptake of G-Quadruplex Ligands Based on Carbohydrate Naphthalene Diimide Conjugates.
abstract: The G-quadruplexes (G4s) are currently being explored as therapeutic targets in cancer and other pathologies. Six carbohydrate naphthalene diimide conjugates (carb-NDIs) have been synthesized as G4 ligands to investigate their potential selectivity in G4 binding and cell penetration. Carb-NDIs have shown certain selectivity for G4 structures against DNA duplexes, but different sugar moieties do not induce a preference for a specific G4 topology. Interestingly, when monosaccharides were attached through a short ethylene linker to the NDI scaffold, their cellular uptake was two- to threefold more efficient than that when the sugar was directly attached through its anomeric position. Moreover, a correlation between more efficient cell uptake of these carb-NDIs and their higher toxicity in cancerous cell lines has been observed. Carb-NDIs seem to be mainly translocated into cancer cells through glucose transporters (GLUT), of which GLUT4 plays a major role.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Instituto de Parasitología y Biomedicina, CSIC, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento, s/n, 18016, Armilla, Granada, Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Arévalo-Ruiz
authors.affiliation: Department of Chemistry, University of Pavia, V.le Taramelli 10, 27100, Pavia, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Doria
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Instituto de Parasitología y Biomedicina, CSIC, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento, s/n, 18016, Armilla, Granada, Spain.
authors.forename: Efres
authors.initials: E
authors.lastname: Belmonte-Reche
authors.affiliation: Institut Européen de Chimie Biologie (IECB), ARNA Laboratory, Université de Bordeaux, Inserm U1212, CNRS UMR5320, 2, rue Robert Escarpit, Pessac, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: De Rache
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Instituto de Parasitología y Biomedicina, CSIC, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento, s/n, 18016, Armilla, Granada, Spain.
authors.forename: Jenny
authors.initials: J
authors.lastname: Campos-Salinas
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Instituto de Parasitología y Biomedicina, CSIC, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento, s/n, 18016, Armilla, Granada, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Lucas
authors.affiliation: Department of Inorganic and Organic Chemistry, University Jaume I, 12071, Castellón, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Falomir
authors.affiliation: Department of Inorganic and Organic Chemistry, University Jaume I, 12071, Castellón, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Carda
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Instituto de Parasitología y Biomedicina, CSIC, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento, s/n, 18016, Armilla, Granada, Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Pérez-Victoria
authors.affiliation: Institut Européen de Chimie Biologie (IECB), ARNA Laboratory, Université de Bordeaux, Inserm U1212, CNRS UMR5320, 2, rue Robert Escarpit, Pessac, France.
authors.forename: Jean-Louis
authors.identifier: http://orcid.org/0000-0003-3043-8401
authors.initials: JL
authors.lastname: Mergny
authors.affiliation: Department of Chemistry, University of Pavia, V.le Taramelli 10, 27100, Pavia, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Freccero
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Instituto de Parasitología y Biomedicina, CSIC, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento, s/n, 18016, Armilla, Granada, Spain.
authors.forename: Juan Carlos
authors.identifier: http://orcid.org/0000-0003-2400-405X
authors.initials: JC
authors.lastname: Morales
keywords: G-quadruplexes; cancer; carbohydrates; glycoconjugates; structure-activity relationships