Selected cytotoxic gold compounds cause significant inhibition of 20S proteasome catalytic activities

Six structurally diverse cytotoxic gold compounds are reported to cause profound and differential inhibition of the three main catalytic activities of purified 20S proteasome whilst auranofin, an established gold(I) drug in clinical use, is nearly ineffective. In particular, the gold(I) complex [(pbiH)Au(PPh3)]PF6, turns out to be the most potent inhibitor of all three enzyme activities with sub-micromolar IC50 values. The present results further support the viewthat proteasome inhibitionmay play amajor – yet not exclusive – role in the cytotoxic actions of gold based anticancer agents.