The mechanism of action of platinum antitumor drugs

Abstract

A discussion is presented on the mechanism of action of platinum amine compounds, used as antitumor drugs. The relationship between biological activity and structure of the compounds is discussed, with special attention to the nature of the ligands coordinated to platinum. The primary biological target appears to be the interaction with nucleic acids, and therefore studies of the interaction of platinum amine compounds (both active and inactive ones) with nucleic acids and nucleic acid fragments are of great interest. Studies on mononucleotides have made clear that a strong preference exists for platinum binding at guanine-N7 sites. Investigations on oligonucleotides have shown that, when two neighboring guanines are present, chelation of the cis-Pt(NH3)2 unit (abbreviated cisplatin) is strongly preferred above all other possibilities. Studies on DNA (in vivo and in vitro) have made clear that similar binding modes occur in DNA and oligonucleotides, and that.sbd.after cisplatin binding.sbd.the DNA structure is distorted in the same way as double-stranded oligonucleotides.