Status of non-classical mononuclear platinum anticancer drug development.

Cisplatin has become one of the most commonly used compounds for the treatment of a wide spectrum of human malignancies. Unfortunately, cisplatin has several major drawbacks. Driven by the impressive impact of cisplatin on cancer chemotherapy, great efforts have been made to develop new derivatives with improved pharmacological properties. Among the over 30 platinum agents which have entered clinical trials after the onset of clinical studies with cisplatin in the early 1970s, only carboplatin and oxaliplatin have received worldwide approval so far, nedaplatin, lobaplatin and heptaplatin have gained regionally limited approval. It has become quite evident that mere analogues of cisplatin or carboplatin will not probably offer any substantial clinical advantages over the existing drugs. Consequently, attention turned to the synthesis of non-classical platinum anticancer drugs which were capable of forming a different range of DNA adducts which could display a different spectrum of anticancer activity compared to cisplatin. The status of non-classical bi- and multi-nuclear platinum anticancer drug development has been reviewed. This review will summarize the structural types and structure-activity of non-classical mononuclear platinum anticancer drugs, and discuss their future potential as anticancer agents.