Choline kinase inhibition and docking studies of a series of 6-(benzylthio)-9 H-purin-9-yl-pyridinium derivatives.

Human choline kinase is a well validated target for the treatment of cancer. In the last two decades, many choline kinase inhibitors have been developed and one of them is currently under evaluation in clinical trials. In this paper a series of 6-(benzylthio)-9 H-purin-9-yl-pyridinium derivatives were evaluated as choline kinase inhibitors, and their effects on cell proliferation were also investigated in the human hepatoma HepG2 cell line. The most potent inhibitor against purified choline kinase-α1 presents an IC value of 0.4 μM. The biological data and the docking studies described here, support that the 4-(dimethylamino)pyridinium cationic head and a small linker (benzene or biphenyl) are the essential structural parameters for choline kinase inhibition of the tested compounds. [ABSTRACT FROM AUTHOR]