Review of gold compounds as next generation potential anticancer drugs

Abstract

Platinum complexes have been used in the treatment of cancer diseases since the 1970s, but the side eff ects and resistance of tumor cells to these drugs have triggered the search for new and improved cytostatic agents. Nowadays, new platinum compounds and other metal complexes, including gold complexes, are tested.Gold (Au, lat. Aurum) has been used in medicine since antiquity. Probably the earliest use was in Chinese medicine for the treatment of smallpox. Currently gold complexes are used as an anti-arthritis medicines. These compounds inhibit lymphocyte proliferation, production of reactive oxygen species in macrophages, and production of interleukin 1. The isotope 198Au (half-life — 2.7 days) is used to treat certain cancers [1].In this review we describe the gold coordination compounds that appear to be very promising as new potential anticancer drugs. Many of the complexes exhibit high antitumour activity and these compounds are active via mechanisms that diff er from those of the Pt(II) antitumour agents such as cisplatin. The anti-arthritic Au(I) phosphine drug, auranofi n, shows high antitumor activity against P388 leukemia cells. It has been shown to induce apoptosis via selective inhibition of the mitochondrial isoform of thioredoxin reductase. This is an enzyme which plays a critical role in the regulation of cancer cell apoptosis, making it an attractive target for the new anticancer drugs. Au(III) complexes are rapidly reduced to Au(I) under physiological conditions, but some Au(III) complexes have been identified which have significant antitumour properties, and in which the Au(III) oxidation state is stabilized by appropriate choice of ligands. These compounds can be used in the treatment of ovarian cancer, hepatocellular carcinoma or nasopharyngeal carcinoma. Similarly to Au(I), the interactions of Au(III) compounds with DNA are very weak, and there is evidence that they induce apoptosis by mechanisms involving mitochondrial cell death pathways.