Disagreement over the anticancer action of ruthenium versus platinum complexes has been settled, claim chemists in Switzerland.

Cisplatin is a widely used platinum-based anticancer drug. The success of this metallopharmaceutical prompted scientists to look for new metal-based medicines, with organometallic ruthenium complexes attracting particular attention. But organometallic ruthenium complexes are structurally quite different to cisplatin, not only at the metal centre but also the groups surrounding the metal.

The structural differences between the ruthenium complexes and cisplatin have prompted questions, and disagreement, over whether the two types of compound work in the same way in the body. Dirk Deubel and colleagues at the Swiss Federal Institute of Technology in Zürich claim to have settled the argument using a computational approach.

The researchers compared computer models that predict the way cisplatin and an organometallic ruthenium compound would react with various biological targets, such as nucleic acids (the building blocks of DNA). 'Both complexes have a remarkably similar reactivity and selectivity to biologically relevant substrates,' said Deubel. In particular, both bind strongly and selectively to the nucleic acid guanine, which would result in cell death, he said.

Deubel said his approach could be used in screening for new metal-based drug candidates. Bernhard Lippert, an expert on metal compound-biomolecule interactions at the University of Dortmund, Germany, said the results should be used cautiously for drug discovery. 'There are so many other factors besides the preferred target molecule which decide on the effectiveness of a particular metal compound,' said Lippert.

James Mitchell Crow