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.