Although platinum-based drugs such as cisplatin are powerful anticancer agents, they have undesirable side effects and are effective against only a few kinds of cancers. There is, therefore, a need for new drugs with an improved spectrum of efficacy and lower toxicity. Complexes of copper, gold and silver (coinage metals) are potential candidates to fulfill this need. The development of anticancer drugs based on these metals is currently a very active field. Considerable effort has also been put into elucidating the mechanisms of action of these complexes and optimizing their bioactivity through structural modification. In this review, we highlight recent developments in the design of coinage metal complexes with anti-tumor activity and discuss the emerging importance of quantitative structure-activity relationship methods in the study of anticancer metal complexes. Future work in this field, including likely coinage metal complexes that will attract attention, are proposed.

Four new derivatives of the type [Au(ppy)X₂] (ppy = 2-phenylpyridine) together with [Au(ppy)Cl₂] (1) have been synthesized and characterized [X = ac = CH₃COO⁻ (2), bz = C₆H₅COO⁻ (3); mal = CH₂(COO⁻)₂ (4), cbdca = C₄H₆(COO⁻)₂ (5)]. The crystal structures of 2 and 3 are similar in which two carboxylate groups are bound to gold through oxygen, but the two Au–O distances are inequivalent. The crystal structure of 5 shows that gold is bound to σ-C,N-phenylpyridine (ppy) and O,O-cbdca, forming a five-membered and a six-membered chelate ring, respectively. In all four structures the Au(III) center exhibits a square planar coordination geometry and the trans influence of the σ-bonded phenyl group is apparent. The σ-bonded phenyl group contributes to stabilizing these complexes in reducing, biological media. The reaction between 5 and chloride has been investigated by ¹H NMR spectroscopy and reveals slow replacement of cbdca by chlorides through an intermediate [Au(ppy)(O-cbdca)Cl]. All five complexes have been tested for cytotoxic properties in vitro against MOLT-4 (human leukemia) and C2C12 (mouse tumour) cell lines. The results show that these complexes have similar cytotoxicity profile to cisplatin against MOLT-4 but are inactive on C2C12, except for complex 5.