The latest anticancer compounds could prove to be effective drugs if they are protected in an organic jacket, claim researchers in Australia. The suggestion is offered by Grant Collins and colleagues from the University of New South Wales, Campbell, as a solution to problems encountered with platinum complexes during clinical trials. 

The complexes, containing two or three platinum centres, work by binding to cell DNA and inhibiting its replication. Preliminary tests have shown that they are more active than some clinically-used drugs and will act against cells that are resistant to drugs such as cisplatin. Unfortunately, their binding properties mean that they also bind to the thiol (-SH) groups of proteins in the bloodstream. Once bound, the complexes degrade to an inactive form, as they lose a ligand that links two platinum centres together. 

Anticancer compounds protected by an organic jacket should prove more effective.

Outlining their method, Collins explained how 'encapsulating the [complexes] inside cucurbiturils, barrel-shaped molecules that can bind guest molecules, is a potential approach to protecting them from reaction with blood proteins.'

The team used NMR spectroscopy to study how the complexes fit inside the cucurbituril molecules. They also used the technique to measure how quickly thiol compounds degrade a complex, by monitoring changes in its spectrum after a thiol, such as cysteine, had been added. The complex was attacked much more slowly once it had been encapsulated, showing that it was being protected by the cucurbituril.

'The high reactivity of platinum complexes in the blood stream and elsewhere is a major cause of drug deactivation and toxic side effects,' said Trevor Hambley, an expert in platinum-based anticancer drugs at the University of Sydney, Australia. The research 'suggests a highly promising approach to reducing these unwanted reactions.'

Rachel Warfield