New trends in platinum and palladium complexes as antineoplastic agents

The discovery of cisplatin (cis-Pt(NH3)2Cl2) as an antineoplastic agent has focussed attention on the rational design of metal complexes that can be potentially used in cancer chemotherapy. Today, the pharmaceutical industry invests more than $1 billion each year in the development of new metal-based drugs to improve biological activities, in terms of cellular selectivity, therapeutic efficiency and minimization of side effects. Chemotherapies based on transition metals play a key role in cancer treatment, and among them platinum and palladium are the most fruitful. This article reviews the main recent advances in the design and synthesis of platinum- and palladium-based drugs, their structural features and biological studies of them. The rationale for the choice of the ligand, related to leaving groups, the geometry of the complex and the oxidation state of the metal ion, is discussed. An overview of the main biological techniques and approaches for testing the interaction of these molecules with the biological environment, mainly DNA, to validate the effect is also provided.