Structural and mechanistic aspects of platinum anticancer agents

After the discovery of the anticancer activity of cisplatin many studies have focused on elucidating its mechanism of action. The antitumor effects of platinum complexes originate from their interaction with DNA, which causes interference with normal transcription or DNA replication. Pt-DNA adducts produced by cisplatin and many of its analogues are almost identical, and would explain their similar patterns of tumor sensitivity and susceptibility to resistance. However, platinum compounds bearing trans-amine (ammine) ligands, and those of multinuclear Pt complexes give rise to radically different DNA-Pt adducts. Platinum-sulfur interactions are associated with undesired phenomena such as resistance and toxicity. Modern multinuclear n.m.r. approaches are very powerful for the investigation of thermodynamics and kinetics of the reactions of metal compounds with biomolecules, and it is possible to study the coordination chemistry of platinum drugs under physiological relevant conditions. In this review biocoordination chemistry of platinum anticancer drugs and various mechanistic aspects related to the antitumor effects of platinum complexes have been explained.