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Nucleic Acids and Molecular Biology 4

Volume 4 of the series Nucleic Acids and Molecular Biology pp 9-38

Interaction of Platinum Antitumor Compounds with DNA

  • C. A. Lepre
  • , S. J. LippardAffiliated withDepartment of Chemistry, Massachussets Institute of Technology

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Abstract

The cis and trans isomers of diamminedichloroplatinum(II) (cis- and trans- DDP, Fig. 1) have enjoyed a long history in inorganic chemistry, having first been synthesized and separated in the 19th century. Until recently, however, complexes of the platinum group metals were of little interest to medicinal chemists owing to their reputation as highly toxic compounds. Interest in the biological effects of platinum complexes was greatly stimulated following reports that cis,-[Pt(NH3)2CI4] and related cis-coordinated platinum ammine chloride complexes induced filamentous growth in Escherichia coli, an indication of DNA damage (Rosenberg et al. 1965; Rosenberg et al. 1967; Rosenberg 1980). Subsequent demonstration that cis-DDP exhibited antitumor activity in mice led to clinical trials and eventual FDA approval for its use as an anticancer drug (Rosenberg et al. 1969; Rosenberg 1980).