Platinum group antitumor chemistry: design and development of new anticancer drugs complementary to cisplatin.

In the next two decades, the world is expected to see around 20 million cases of cancer. Moreover, the types of cancer will vary considerably from country to other. Therefore, all efforts will be needed to face such a vast diversity of problems. With current annual sales of about $500 millions, the platinum(II) complex known as cisplatin [cis-(NH3)2PtCl2] is still one of the most effective drugs to treat testicular, ovarian, bladder and neck cancers. Since it was launched in 1978 there has been a rapid expansion in research to find new, more effective metal-based anticancer drugs and to study their interactions with biological systems. This study gives an up to date overview of the anticancer chemistry of the platinum group elements platinum, palladium, and nickel with an emphasis on the new strategies used in the development of new antitumor agents. Methodologies for application of bulky aromatic or aliphatic nitrogen ligands, chiral organic moieties, chelates containing other donor atoms than nitrogen, and biologically active ligands in the design of agents analogous to cisplatin are presented. The review also aims to highlight the class of the unconventional complexes that violate the empirical structure-activity rules (SAR) of platinum compounds and the common features and structural differences between the most successful anticancer complexes that are currently in human clinical trials.