Gold compounds as anticancer agents: chemistry, cellular pharmacology, and preclinical studies.

摘要

Gold compounds are a class of metallodrugs with great potential for cancer treatment.\udDuring the last two decades, a large variety of gold(I) and gold(III) compounds are reported to possess\udrelevant antiproliferative properties in vitro against selected human tumor cell lines, qualifying themselves\udas excellent candidates for further pharmacological evaluation. The unique chemical properties of\udthe gold center confer very interesting and innovative pharmacological profiles to gold-based\udmetallodrugs. The primary goal of this review is to define the state of the art of preclinical studies on\udanticancer gold compounds, carried out either in vitro or in vivo. The available investigations of\udanticancer gold compounds are analyzed in detail, and particular attention is devoted to underlying\udmolecular mechanisms. Notably, a few biophysical studies reveal that the interactions of cytotoxic gold\udcompounds with DNA are generally far weaker than those of platinum drugs, implying the occurrence\udof a substantially different mode of action. A variety of alternative mechanisms were thus proposed, of\udwhich those involving either direct mitochondrial damage or proteasome inhibition or modulation of\udspecific kinases are now highly credited. The overall perspectives on the development of gold compounds\udas effective anticancer drugs with an innovative mechanism of action are critically discussed on\udthe basis of the available experimental evidence.