G-quadruplexes (G4) are currently being explored as therapeutic targets in cancer and other pathologies. We have synthesized six carbohydrate naphthalene diimide conjugates (carb-NDIs) as G4 ligands to investigate their potential selectivity on G4 binding and on cell penetration. Carb-NDIs have shown certain selectivity for G4 structures against DNA duplexes but the different sugar moieties did 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 2-3 fold more efficient than when the sugar was directly attached through its anomeric position. Moreover, a correlation between the 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 the cancer cells through glucose transporters where GLUT4 plays a major role.
Synthesis, Binding Properties, and Differences in Cell Uptake of G-Quadruplex Ligands Based on Carbohydrate Naphthalene Diimide Conjugates
DORIA, FILIPPOInvestigation
;FRECCERO, MAURO
Writing – Original Draft Preparation
;
2017-01-01
Abstract
G-quadruplexes (G4) are currently being explored as therapeutic targets in cancer and other pathologies. We have synthesized six carbohydrate naphthalene diimide conjugates (carb-NDIs) as G4 ligands to investigate their potential selectivity on G4 binding and on cell penetration. Carb-NDIs have shown certain selectivity for G4 structures against DNA duplexes but the different sugar moieties did 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 2-3 fold more efficient than when the sugar was directly attached through its anomeric position. Moreover, a correlation between the 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 the cancer cells through glucose transporters where GLUT4 plays a major role.File | Dimensione | Formato | |
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Arevalo_et_al-2016-Chemistry_-_A_European AAM.pdf
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Descrizione: AAM Chem. Eur. J. 10.1002/chem.201604886
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