Platinum Anticancer Prodrugs A Photoactivation Strategy

A redox activation mechanism usually involves a change in oxidation state of the metal (but could also be ligand-centered). Typically, the oxidation state changes from a state in which 

Pt(TV) Prodrugs. Platinum(IV) complexes have been widely studied as potential prodrugs that avoid the limitations of the cisplatin class of anticancer drugs. Indeed, the Pt(IV) compound satraplatin [Pt(cha)Cl2(OAc)2(NH3)] (cha, cyclohexylamine) is currently in clinical trials for treatment of hormone-refractory prostate cancer (Fig. 1) (22). Satraplatin is the first orally bioavailable platinum derivative under active clinical investigation and is particularly attractive because of the convenience of administration, milder toxicity profile, and lack of cross-resistance with cisplatin. These results are promising and support the idea that platinum(IV) complexes offer the opportunity to overcome some of the problems associated with cisplatin and its analogs. 

An interesting alternative mechanism of activation is the photochemical reduction of Pt(IV) to Pt(II) (Fig. 3). In addition to photoreduction, photosubstitution and photoisomerization can also occur, making the photochemistry of Pt complexes difficult to predict and a careful analysis of the photoproducts imperative (21). We have been involved particularly in the development of photochemotherapeutic agents based on Pt(IV) and the study of their photodecomposition and (subsequent) interactions with 

Ultimately, for Pt(IV) anticancer drugs, a combination of incorporation of bioactive ligands that specifically target cancer cells, control over ligand-exchange kinetics, and selective activation by light would allow for temporal and spatial control of drug delivery and activation. 

Pt(TV)-Iodido Complexes. The first photoactive Pt(IV) prodrugs were reported by Bednarski et al. in the 1990s (23). The complex 

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