News from across RSC Publishing.
Stepping up the fight against malaria
15 December 2006
Simple synthetic analogues of a Chinese herbal medicine could help tackle the spread of drug-resistant malaria.
Highly bioactive derivatives of artemisinin, a natural product used for centuries in China to treat malaria, have been made by UK chemists. The team, led by Paul O'Neill at the University of Liverpool, made several new derivatives that are even more active than the natural product, but have a simpler structure and are entirely synthetic.
Artemisinin-based drugs are the current medicine of choice for treating resistant strains of the malaria parasite. As resistance to traditional antimalarials like chloroquine has become more widespread, demand for artemisinin has outstripped supply. This shortage, combined with the cost of the drug, has pushed chemists to look for cheap synthetic alternatives with similar bioactivity, said O'Neill.
The oxygen-rich endoperoxide (shown in red) is the key to antimalarial activity
The new analogues developed by O'Neill's team incorporate an oxygen-rich heterocycle called an endoperoxide, a component also found in the natural product. 'The presence of an endoperoxide in artemisinin is pivotal to its activity as an antimalarial,' said John Snaith, an expert in bioactive heterocycles at the University of Birmingham, UK.
'The challenges in the future will involve maximising the stability and oral bioavailability of candidate molecules, reducing the number of synthetic steps and developing a chemical process for large-scale synthesis,' said O'Neill.
James Mitchell Crow
Design and synthesis of orally active dispiro 1,2,4,5-tetraoxanes; synthetic antimalarials with superior activity to artemisinin
R Amewu, A V Stachulski, S A Ward, N G Berry, P G Bray, J D, G Labat, L Vivas and P M O'Neill, Org. Biomol. Chem., 2006, 4, 4431.