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

Abstract

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

Exploring the biochemical mechanisms of cytotoxic gold compounds: a proteomic study

“…Accordingly, our laboratories have developed a variety of structurally diverse gold(III) compounds as potential chemotherapeutic leads [4]. We previously reported that one of these complexes, namely, the binuclear gold(III) complex Auoxo6, manifests very encouraging cytotoxic properties in vitro and constitutes a new promising chemotherapeutic lead [5,6].…”

Gold(III)‐dithiocarbamato anticancer agents: Activity, toxicology and histopathological studies in rodents

“…Moreover, gold(III) complexes show chemical features that are very close to those of clinically established platinum(II) derivatives, such as the preference for squareplanar coordination and the typical d 8 -electronic configuration, making them very attractive for testing as antineoplastic drugs. [8][9][10] …”

“…Moreover, gold(III) complexes show chemical features that are very close to those of clinically established platinum(II) derivatives, such as the preference for squareplanar coordination and the typical d 8 -electronic configuration, making them very attractive for testing as antineoplastic drugs. [8][9][10] In this context, several gold(III)-dithiocarbamato derivatives have been designed and tested by our research group as potential anticancer agents. [11][12][13] In particular, some showed promising and outstanding properties in terms of greater in vitro and in vivo antitumor activity than cisplatin, and their capability to overcome both acquired and intrinsic resistance showed by some types of tumors toward the reference drug suggests that different mechanisms of action and biological targets may be involved.…”

Mass spectrometry as a powerful tool to study therapeutic metallodrugs speciation mechanisms: Current frontiers and perspectives

“…In the 1980s, the gold(I) coordination complex auranofin [(2,3,4,6-tetra-O-acetyl-1-(thio-kS)--Dglucopyranosato)(triethylphosphine) Au(I)] (Figure 1), was found to be highly cytotoxic to tumour cells in vitro, opening the way to the evaluation of a range of Au(I) phosphine-based complexes for anticancer applications. [27,28] In parallel, gold(III) complexes were investigated as potential antitumor compounds, based on the idea that square planar Au(III) d 8 compounds are isoelectronic and isostructural with Pt(II), thus potentially mimicking the cisplatin's activity and ability to react with DNA. [29,30] Thus, the renaissance of interest for gold compounds as potential anticancer metallodrugs has resulted, in the course of the last decade, in the synthesis of a number of structurally diverse gold(I) and gold(III) species, endowed with sufficient chemical stability and with relevant antiproliferative activities.…”