Tuning the metabolism of the anticancer drug cisplatin with chemoprotective agents to improve its safety and efficacy

Abstract

Numerous in vivo studies have shown that the severe toxic side-effects of intravenously administered cisplatin can be significantly reduced by the co-administration of sulfur-containing ‘chemoprotective agents’. Using a metallomics approach, a likely biochemical basis for these potentially useful observations was only recently uncovered and appears to involve the reaction of chemoprotective agents with cisplatin-derived Pt-species in human plasma to form novel platinum–sulfur complexes (PSC's). We here reveal aspects of the structure of two PSC's and establish the identification of an optimal chemoprotective agent to ameliorate the toxic side-effects of cisplatin, while leaving its antineoplastic activity largely intact, as a feasible research strategy to transform cisplatin into a safer and more effective anticancer drug.