Impact of Chemical Structure and Hydrolysis Mechanisms on the Pharmacological Effects and Toxicity Profiles of Licensed Platinum-Based Drugs

Resistance and toxicity remain major challenges in platinum-based anticancer therapies. This study aims to compare how the chemical structure and hydrolysis mechanisms influence the pharmacological activity and toxicological profiles of approved platinum drugs: Cisplatin, Carboplatin, Oxaliplatin, Nedaplatin, Lobaplatin, Heptaplatin, and Satraplatin. Carboplatin and Nedaplatin undergo hydrolysis via a two-step hydration process, ultimately generating the same active species as Cisplatin, namely diaquadiamine-platinum. In contrast, Oxaliplatin, Lobaplatin, Heptaplatin, and Satraplatin share a hydrolysis mechanism in which the first step involves ring-opening and addition of a water molecule, followed by ligand loss and formation of the di-aquated product through a second water addition. Regarding toxicity, Cisplatin, Carboplatin, and Oxaliplatin exhibit nephrotoxic effects, while Cisplatin and Heptaplatin are particularly nephrotoxic. Myelosuppression represents the primary dose-limiting toxicity for Carboplatin, Oxaliplatin, Nedaplatin, Lobaplatin, and Satraplatin.