Recent developments in antitumour platinum coordination compounds

Abstract

The square planar platinum(II) complex, cisplatin, is among the most valuable drugs for the treatment of testicular, ovarian, bladder, head and neck cancers and other solid tumours. The major setbacks of cisplatin, namely its significant toxicological profile and the occurrence of primary or acquired resistance, have stimulated extensive research to discover new, more effective and/or better tolerated platinum-based chemotherapeutics. These efforts have resulted in the successful development and commercialisation of five clinically utilised cisplatin analogues: carboplatin, oxaliplatin, nedaplatin, lobaplatin and heptaplatin. Unfortunately, none of the successors of cisplatin could be considered superior to the prototype in terms of both lower toxicity and clinical efficacy and, thus, the pursuit for novel platinum complexes with optimised pharmacological profile remains an unsolved problem. The present drug design strategies are based on more elaborate and rational approaches aimed at reductiing the reactivity with non-pharmacological targets, tumour-targeting and/or the development of analogues with cisplatin-alternative mode of DNA-binding. This review gives an up-to-date overview of these approaches for the optimisation of platinum anticancer drugs with an emphasis on recent developments.