0000000000769217
AUTHOR
Maria Agostina Cinellu
Selected cytotoxic gold compounds cause significant inhibition of 20S proteasome catalytic activities
Abstract 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 ( PPh 3 )] PF 6 , turns out to be the most potent inhibitor of all three enzyme activities with sub-micromolar IC 50 values. The present results further support the view that proteasome inhibition may play a major – yet not exclusive – role in the cytotoxic actions of gold based anticancer agents.
Gold(I) compounds with lansoprazole-type ligands
A number of gold(I) complexes containing the proton pump inhibitor (PPI) lansoprazole and its reduced precursor 2-((3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl)methylthio)-1H-benzo[d]imidazole have been synthesized and their biological effects have been evaluated in human cancer and nontumorigenic cells in vitro. The lansoprazole-based compounds appear to act through a V-H+-ATPase-mediated mechanism.