Deubiquitinases as Anticancer Targets of Gold Complexes.

Metal-based anticancer agents with non-DNA targets are anticipated for overcoming cisplatin resistance problems. Gold complexes are generally known to undergo ligand exchange or redox reactions with thiols, and hence, are potentially useful agents that could target thiol-containing enzymes, but not DNA. Recent studies have shown that deubiquitinases (DUBs), key enzymes regulating proteasome-related protein homeostasis, are potential anticancer targets of both gold(I) and gold(III) complexes. In this review, the current status of gold complexes as DUB inhibitors is discussed. In particular, auranofin and cyclometalated gold(III) complexes containing dithiocarbamate ligands (e.g., [(AuIII(C N)(DEDT)]+, HC N=2-phenylpyridine, DEDT=diethyldithiocarbamate) are highlighted as examples of DUB inhibitors. The mechanisms of their anticancer action, together with in vitro and/or in vivo antitumor potencies, are also explored. [ABSTRACT FROM AUTHOR]