Synthesis, Binding Properties, and Differences in Cell Uptake of G-Quadruplex Ligands Based on Carbohydrate Naphthalene Diimide Conjugates

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...

Descripción completa

Detalles Bibliográficos
Autores: Arévalo-Ruiz, Matilde, Doria, Filippo, Belmonte-Reche, Efres, De Rache, Aurore, Campos-Salinas, Jenny, Lucas, Ricardo, Falomir, Eva, Carda, Miguel, Pérez-Victoria, José M., Mergny, Jean-Louis, Freccero, Mauro, Morales, Juan Carlos
Tipo de recurso: artículo
Estado:Versión enviada para evaluación y publicación
Fecha de publicación:2017
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/159375
Acceso en línea:http://hdl.handle.net/10261/159375
Access Level:acceso abierto
Descripción
Sumario: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.

Similares en LA Referencia