Glycoconjugate coumarins exploiting metabolism-enhanced fluorescence and preferential uptake: New optical tools for tumor cell staining

The possibility to visually discriminate cells based on their metabolism and capability to uptake exogenous molecules is an important topic with exciting fallback on translational and precision medicine. To this end, probes that combine several complementary features are necessary. The ideal probe is selectively uptaken and activated in tumor cells compared with control ones and is not fluorescent in the extracellular medium. Fluorogenic compounds that combine enzyme-activated pH sensitivity and good cell uptake can be an ideal solution, provided that the sensed enzymes are dysregulated in tumor cells. Here, we present synthesis and in vitro evaluation of a new class of glyco-coumarin based probes that merge all these features. These probes show uptake ratio in tumor vs. control cells up to 3:1, with a cell to background ratio upon administration of the probe up to 5:1. These features make this new family of fluorogenic targeted probes a promising tool in life science.