US chemists have adapted a Chinese herbal medicine to create a new generation of antimalarial drugs which could solve some of the current crop's failings. 

Gary Posner and colleagues from Johns Hopkins University, Maryland, US, announced trial results showing their compounds, trioxanes, are potent enough to cure malaria-infected mice with a single low dose.

The new drugs were all created by pairing up molecules of artemisinin - a natural product used for centuries in China to treat malaria. Artemisinin-based treatments are already considered the best way to tackle resistant strains of the malaria parasite, via a combination therapy. 

'But no artemisinin-based drugs or synthetic trioxanes have been reported with potency close to that of our dimer compounds,' says Posner. The dimers seem to bypass the failings of current monomeric artemisinin-based treatments, which have to be administered in multiple doses (and in combination with other drugs) to kill parasites because they quickly break down in the blood.  

The new dimers are either so potent that they clear all the parasites before being metabolised, thinks Posner, or they last longer in the blood. That's what the researchers were aiming for: they intentionally made their dimer structures more resistant to hydrolysis by replacing a vulnerable acetal linkage with a stronger carbon-carbon bond.

Though the dimers' safety hasn't yet been thoroughly tested, their early promise also extends to cancer treatment, says Posner. 

'I do think it potentially represents a big step forward,' commented Donald Krogstad, from the Department for Tropical Medicine at Tulane University, New Orleans. He points out that the easy synthesis from artemisinin is particularly attractive.

The new compounds have lots of competition, not least from entirely synthetic antimalarial drugs which mimic the artemisinin peroxide core. But one of those, OZ-277, has recently run into the types of bioavailability problems which Posner hopes to avoid. Medicines for Malaria Venture (MMV), who had co-funded the development of OZ-277 into Phase II trials with Indian-based firm Ranbaxy, have decided to stop funding the project. Joerg Moehrle, Director of Clinical Development at MMV, said data showed the drug was too unstable in the red blood cells of patients infected with malaria. Jonathan Vennerstrom, of the University of Nebraska Medical Center, Omaha, US, whose team initially developed OZ-277, said he was now looking into second-generation drugs which lasted longer in malaria patients.

Richard Van Noorden