New Approaches to the Design of Platinum Antitumor Agents
In the years since the discovery of cisplatin, the search for new platinum-based antitumor agents has grown at a staggering rate. Several thousand platinum complexes have been prepared and screened in laboratories throughout the world in an effort to develop new platinum drugs with improved therapeutic properties. In many respects these efforts have been rewarded, as second generation analogs such as carboplatin are now proving to be successful clinical agents.1 However, the majority of the new compounds2 that have been identified from these studies are close relatives of cisplatin from a structural point of view and, by virtue of this fact, these agents are similar in terms of their mechanism of action.3 Consequently, clinical expectations for new platinum antitumor agents remain somewhat tempered by the narrow class of compounds that have been identified from drug discovery efforts. While basic improvements in pharmacology and toxicology have been made by altering the reactivity and lipophilicity of the cisplatin analogs, little progress has been made in altering the spectrum of activity displayed by these complexes. One approach to solving this problem is to look beyond the structural relatives of cisplatin by identifying novel materials that can be utilized as building blocks for new classes of platinum antitumor agents.
KeywordsAntitumor Agent Platinum Complex Platinum Drug Drug Discovery Effort Carbodiimide Coupling
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