Bioinorganic Chemistry: The Study of the Fate of Platinum-Based Antitumour Drugs

Elisabetta      Gabano; Mauro      Ravera; Donato      Colangelo; Domenico      Osella

Abstract

The history of inorganic pharmacology can be traced to antiquity with the medicinal use of inorganic salts, coordination and organometallic compounds. The clinical applications of metal-based drugs today are limited, but extremely significant. The most common metallo-therapeutic drugs are platinum, gold and bismuth compounds used in anticancer protocols and in the treatment of rheumatoid arthritis and gastric and duodenal ulcers, respectively. Platinum(II)-derivatives are the most widely prescribed anticancer agents, especially for polychemotherapy. Years of clinical experience have yielded detailed information about the quantitative structure-activity relationship (QSAR), pharmacokinetics and mechanisms of action of Pt-drugs. The accuracy of this information depends on precise measurement of Pt levels in body fluids, tissues, cells and DNA. Inductively Coupled Plasma - Mass Spectrometry (ICP-MS) offers higher sensitivity and accuracy than conventional analytical techniques, making it possible to detect trace concentrations of Pt-drugs at truly pharmacological concentrations. Increased knowledge about the action and fate of Pt-drugs may lead to important insights for the development of new metallo-pharmaceuticals with even wider applications.

Keywords: Antiproliferative agents, platinum complexes, cytotoxicity, pharmacokinetics, ICP-MS determination

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