Gold(III) compounds as anticancer agents: Relevance of gold-protein interactions for their mechanism of action.

摘要: Gold(III) compounds constitute an emerging class of biologically active substances, special interest as potential anticancer agents. During the past decade a number structurally diverse gold(III) complexes were reported to be acceptably stable under physiological-like conditions and manifest very promising cytotoxic effects against selected human tumour cell lines, making them good candidates anti-tumour drugs. Some representative examples will described in detail. There is considerable understanding precise biochemical mechanisms these novel Based on experimental evidence collected so far we hypothesize that metallodrugs, at variance with classical platinum(II) drugs, produce most cases their growth inhibition through variety "DNA-independent" mechanisms. Notably, strong selenoenzyme thioredoxin reductase associated disregulation mitochondrial functions clearly documented some cases, thus providing solid basis for pronounced proapoptotic effects. These observations led us investigate detail reactions few model proteins order gain molecular-level information possible interaction modes protein targets. Valuable insight formation nature gold-protein adducts was gained ESI MS (electrospray ionization mass spectrometry) spectrophotometric studies appropriate systems it exemplified here by two cytochrome c ubiquitin. The mechanistic relevance gold(III)-induced oxidative damage direct gold coordination sidechains specifically assessed. Perspectives future this topics are briefly outlined.