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.
The copper(ii) complexes of two salicylaldehyde semicarbazones, HOC(6)H(4)CH[double bond, length as m-dash]N-NHCONR(2) [H(2)Bnz(2) (R = CH(2)Ph) and H(2)Bu(2) (R = Bu)], were evaluated for their DNA binding and cleavage properties by spectrophotometric DNA titration, ethidium bromide displacement assay and electrophoretic mobility shift assay. Results showed that the Cu(ii) complexes can bind to DNA via a partial intercalation mode with binding constants of 1.1 × 10(4) and 9.5 × 10(3) M(-1) for [Cu(HBnz(2))Cl] and [Cu(HBu(2))Cl], respectively. These complexes also cleave DNA in the presence of ascorbic acid, most likely through hydroxyl radicals that are generated via the reduction of a Cu(ii) to a Cu(i) species. The complexes show similar DNA cleavage activity, which is reflected in the similarity of their frontier molecular orbital energies calculated by density functional theory. These results are discussed in relation to the anticancer properties of the complexes.
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