The chemistry of platinum antitumour agents

  • M. J. Abrams


The vast majority of clinically used antitumour drugs are either synthetic or natural product based organic compounds. The platinum antitumour agents are unique in that they are coordination complexes. The parent compound of this class, cis-diamminedichloroplatinum(II) (cisplatin), contributes to the curative treatment of testicular teratoma and has significant activity against ovarian, head and neck, bladder, cervical and lung cancers. The compound is also highly toxic with the list of side effects including renal damage, severe nausea and vomiting, myelosuppression, ototoxicity and neurotoxicity. Since the antitumour properties of cisplatin were reported by Rosenberg and coworkers in 1969, well over 1000 platinum analogues have been tested for antitumour activity1,2. The goal of this work has been to find analogues with reduced toxicity and/or wider spectrum of activity. Active cisplatin analogues are generally neutral platinum complexes containing two ammine (NH3) or amine ligands in a cis configuration in concert with two (for Pt(II) analogues) or four (for Pt(IV) compounds) relatively labile halide or oxygen ligands3. Complexes with amine groups in a trans configuration are invariably inactive4. Structure-activity relationships (in animal tumour models) and the clinical aspects of platinum drugs have been reviewed2–6.


Trans Isomer Platinum Complex Platinum Drug Alkali Metal Salt Sodium Diethyldithiocarbamate 
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  • M. J. Abrams

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