Chapter

Metallopharmaceuticals I

Volume 1 of the series Topics in Biological Inorganic Chemistry pp 1-43

Anticancer Activity of Cisplatin and Related Complexes

  • Andrew GelascoAffiliated withDepartment of Chemistry, Massachusetts Institute of Technology
  • , Stephen J. LippardAffiliated withDepartment of Chemistry, Massachusetts Institute of Technology

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Abstract

Cisplatin is a simple inorganic compound which has proved to be a very effective anticancer drug, especially against testicular tumors. The compound has therapeutic limitations based primarily on toxic side effects and acquired resistance. The mechanism of action of cisplatin is under intense study in order to understand the chemical basis for these limitations and to develop in a rational manner a new generation of platinum-based antitumor drugs. These studies have led to the discovery of new classes of anticancer platinum compounds, including some which utilize both mononuclear and dinuclear Pt(II) and trans-Pt(IV)geometries. High-resolution structures of cisplatin and derivatives bound to duplex DNA have been determined both by X-ray crystallography and by NMR solution methods. Also noteworthy is the discovery of DNA-binding proteins that specifically recognize cisplatinmodified DNA. The contributions of each of these different areas of study towards an understanding of the molecular mechanism of the anticancer activity of cisplatin are discussed.

Keywords

Cisplatin Anticancer DNA HMG-domain proteins Platinum drugs