Synthesis, Binding Properties, and Differences in Cell Uptake of G-Quadruplex Ligands Based on Carbohydrate Naphthalene Diimide Conjugates
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- 作者：Matilde Aré ; valo-Ruiz ; Dr. Filippo Doria ; Efres Belmonte-Reche ; Dr. Aurore De Rache ; Dr. Jenny Campos-Salinas ; Dr. Ricardo Lucas ; Dr. Eva Falomir ; Dr. Miguel Carda ; Dr. José ; Marí ; a Pé ; rez-Victoria ; Dr. Jean-Louis Mergny ; Prof. Mauro Freccero and Dr. Juan Carlos Morales
- 刊名：Chemistry - A European Journal
- 出版年：2017
- 出版时间：February 10, 2017
- 年：2017
- 卷：23
- 期：9
- 页码：2157-2164
- 全文大小：1442K
- ISSN：1521-3765
文摘
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.