RESUMEN

Caged ceramide analogues (C6-, C16-, C18-, C22- and C24-Cer) have been prepared by introducing a hydrophilic coumarin-based cage bearing a short polyethylene glycol (PEG) chain. (6-Bromo-7-mTEGylated-coumarin-4-yl)methyl (Btc) caged ceramide showed efficient photo-uncaging to release the parent ceramide upon direct exposure to 350 nm UV light; in contrast (7-mTEGylated-coumarin-4-yl)methyl (Tc) caged ceramide was photolysed more slowly. In preliminary experiments, Btc-caged ceramides were taken up by cells and their photolysis led to decreases in cell viability, but not to activation of caspase enzymes, suggesting that either reactive oxygen species or an alternate caspase-independent pathway may be responsible for the decreases in cell viability caused by photolysis of caged ceramides.

Asunto(s)

Ceramidas/farmacología , Ceramidas/efectos de la radiación , Cumarinas/química , Fotólisis/efectos de la radiación , Polietilenglicoles/química , Rayos Ultravioleta , Caspasas/metabolismo , Supervivencia Celular/efectos de los fármacos , Ceramidas/síntesis química , Ceramidas/química , Células HeLa , Humanos , Estructura Molecular , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad , Células Tumorales Cultivadas