6-Sulphonate glucose derivatives as potential kinase inhibitors

Protein kinases are enzymes involved in the regulation of many crucial cellular processes like proliferation, differentiation and apoptosis. Among them, the serine/threonine protein kinase B (PKB), also known as Akt, plays a key role as a component of the phosphoinositide 3-kinase (PI3K)-Akt-mTOR axis, which is implicated in abberrant tumor cell signaling. Inappropriate activation of the Akt kinase is a common event in human tumors and Akt is a critical player in cell survival. Thus, inhibitors that target PI3Ks and its downstream effectors, including PKB are potentially relevant for cancer therapy. PI3K activation generates 3-phosphorylated phosphatidylinositols [PI(3)P] that bind PKB plekstrin homology (PH) domain promoting PKB activation through its translocation from the cytosol to the plasma membrane, conformational change and final phosphorilation. Given the structural similarity between inositol and glucose, a series of glucose derivatives as mimics of phosphatidylinositols have been synthesized and evaluated in vitro fr their activity against PKB.