Synthesis, Binding Properties, and Differences in Cell Uptake of G‐Quadruplex Ligands Based on Carbohydrate Naphthalene Diimide Conjugates
- 7 December 2016
- journal article
- research article
- Published by Wiley in Chemistry – A European Journal
- Vol. 23 (9) , 2157-2164
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.Keywords
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