Characterization of platinum(II) complexes exhibiting inhibitory activity against 20S Proteasome

Proteasome inhibitors are useful for biochemical research and clinical treatment. In our previous study, we reported that the 4N-coordinated platinum complexes with anthracene and heterocycle exhibited proteasome inhibitory activity. In the present study, the structure-activity relationships and characterization of these complexes were determined for elucidation of role of aromatic ligands. Lineweaver-Burk analysis revealed that the chemical structure of heterocyles affects binding mode of platinum complexes. Platinum complexes with anthracene and pyridine showed competitive inhibition although platinum complexes with antharcene and phenantholine showed non-competitive inhibition. The structure-activity relationships demonstrated that anthracene moiety play a crucial role for proteasome inhibitory activity. The platinum complexes with naphthalene or benzene exhibited lower inhibitory activities than the platinum complex with anthracene. The reactivity with N-acetyl cysteine varied according to the chemical structure of complexes.