Synthesis of anionic glycolipid fluorescent probes targeting protein kinase B (AKT)

The protein kinase B (PKB or Akt), phosphorylates different protein substrates to promote diverse cellular responses. Inappropriate activation of the PI3K/Akt pathway has been linked to the development of several human pathological states. In addition, the available evidence supports that Akt is a critical player in the development, growth, and drug resistance of cancers. Blockage of Akt signalling can result in apoptosis and growth inhibition of tumour cells with elevated Akt activity. Thus, inhibitors that target PI3Ks and its downstream effectors, including Akt are potentially relevant for cancer therapy. New synthetic anionic glycoglycerolipids 2, derived from the sulfoquinovosyl acylglycerol (SQAG) analogues 1, are currently investigated as potential Akt inhibitors, their structure being easily reconducted to 3-phosphorylated phosphatidylinositols (PI3P), the natural activators of Akt. Some of the prepared compounds 2 resulted active both in isolated enzyme and in cell systems. According to their structures, here we report the syntesis of some fluorescent derivatives (3) as probes for future studies on the cellular distribution and mechanism of action of this class of new potential Akt inhibitors.