Potential for anti-tumour drugs
A team of European researchers has made exciting progress towards a new class of drugs to treat cancer.
The potential drug molecule is a ruthenium complex and from initial studies it looks to compete with existing transition metal anti-tumour agents. One such rival being the widely used platinum compound cisplatin.
Jan Reedijk and colleagues from the University of Leiden, the Netherlands, and the University of Ioannina, Greece, designed the molecule using their knowledge of similar cytotoxic compounds. The ruthenium complex was screened in two cancer cell lines, including one cell line known to be resistant to cisplatin. In both in vitro experiments there was strong cytotoxic activity. The most encouraging result for the scientists is the unprecedented activity of their potential drug in the cisplatin-resistant cell line.
Another factor incorporated into the complex's design is the binding of nitric oxide (NO) to the ruthenium centre. NO is biochemically important and known to play a role in defence mechanisms against tumours. Therefore, new drugs that can supply and control NO levels are of great interest. Reedijk's group has shown that NO is bound to the metal centre but can be released when light is used to irradiate the molecule.
The next step is to combine the molecule's cytotoxicity with its photoactive NO release by irradiating the cell lines with light during the treatment with the ruthenium compound. The release of NO during the in vitro experiment should further enhance the cytotoxic activity of the compound.
The researchers show that the ruthenium complex can bind to DNA and the challenge for them now is to look at the effect of irradiating the molecule while it is bound to DNA. Reedijk says the initial results are 'very promising'.