Synthesis, Binding Properties, and Differences in Cell Uptake of G-Quadruplex Ligands Based on Carbohydrate Naphthalene Diimide Conjugates
Por:
Arévalo-Ruiz M, Doria F, Belmonte-Reche E, De Rache A, Campos-Salinas J, Lucas R, Falomir E, Carda M, Pérez-Victoria JM, Mergny JL, Freccero M and Morales JC
Publicada:
1 feb 2017
Categoría:
Chemistry (miscellaneous)
Resumen:
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.
Filiaciones:
Arévalo-Ruiz M:
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
Doria F:
Department of Chemistry, University of Pavia, V.le Taramelli 10, 27100, Pavia, Italy
Belmonte-Reche E:
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
De Rache A:
Institut Européen de Chimie Biologie (IECB), ARNA Laboratory, Université de Bordeaux, Inserm U1212, CNRS UMR5320, 2, rue Robert Escarpit, Pessac, France
Campos-Salinas J:
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
Lucas R:
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
:
Department of Inorganic and Organic Chemistry, University Jaume I, 12071, Castellón, Spain
Carda M:
Department of Inorganic and Organic Chemistry, University Jaume I, 12071, Castellón, Spain
Pérez-Victoria JM:
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
Mergny JL:
Institut Européen de Chimie Biologie (IECB), ARNA Laboratory, Université de Bordeaux, Inserm U1212, CNRS UMR5320, 2, rue Robert Escarpit, Pessac, France
Freccero M:
Department of Chemistry, University of Pavia, V.le Taramelli 10, 27100, Pavia, Italy
Morales JC:
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
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