Iminosugar Analogues of Phosphatidyl Inositol as Potential Inhibitors of Protein Kinase B (Akt)

A small virtual library of iminosugar derivatives was evaluated by docking experiments carried out by sampling a protein region corresponding to the phosphoinositide binding site of the PH domain of Akt. Four compounds were selected and efficiently synthesised from a common precursor. All compounds were subjected to preliminary biological evaluation on purified enzyme, and - among them - compound 9 exhibited the best inhibitory activity. A small virtual library of iminosugar-based Akt inhibitors have been designed and evaluated by using docking calculations. Selected compounds have been conveniently synthesised, and preliminary biological evaluation identified compound 9 as a possible lead compound for further development of iminosugar-based Akt inhibitors.