N-halogen succinimides : alternative oxidants of platinum anticancer agents

Platinum(II) complexes such as cisplatin have been largely successful in the treatment of cancers, although their low specificity and high toxicity restrict their use.[1–5] This has compelled researchers to develop platinum(IV) analogues of these compounds, to allow fine tuning of the pharmacokinetics to increase activity through targeting.[6,7] These PtIV analogues act as prodrugs, reducing intracellularly to generate the active PtII form, meaning that reduction potential influences cytotoxicity.[8,9] The use of N-halogen succinimide (NXS) as both an oxidising reagent and a source of halogens was first reported in 2010 and has since been used to synthesise both asymmetric and symmetric anticancer complexes.[10–14] The production of asymmetric compounds offers a further mechanism with which pharmacokinetics can be finely tuned. Previously PtII has been oxidised via hydrogen peroxide or using chlorine gas, which typically form symmetric compounds, offering less functional flexibility than asymmetric synthesis.[15] The reduction mechanism of these asymmetric complexes is different to their symmetric counterparts, making it faster and irreversible, which may be advantageous for the pharmacokinetics of the resulting complex as an anticancer agent.[11]