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'Powerful' new way to produce malaria drug is discovered

Scientists have discovered a new way of making a drug commonly used in the fight against malaria around the world.

The method, devised by r esearchers at Cardiff University, South Wales, significantly reduces the time, and cost, taken to produce artemisinin, which is recommended by the World Health Organisation for treatment of all cases of severe malaria and works by attacking all stages of the malaria parasite in the blood.

Discovered by Chinese scientist Tu Youyou, who was awarded the Nobel Prize in Physiology or Medicine in October 2015 for the find, the worldwide supply of artemisinin relies predominantly on the extraction of the product from the plant Artemisia annua.

Extracting the drug is a lengthy process, which consists of 13 steps, so chemists began looking at a way of efficiently producing it in a laboratory.

There is an urgent need to produce the drug at low cost, because the current demand for artemisinin comes mainly from the developing world.

Professor Rudolf Allemann, head of the university's School of Chemistry and lead author of the research, said: "Our new method has essentially bypassed a number of key steps on the way to producing artemisinin.

"What we're left with is a novel and powerful approach for producing the drug that does not rely on extraction from large amounts of plants. Our approach could reduce market fluctuations in the supply chain of artemisinin."

The method reverses part of the production process seen in nature and means artemisinin can be created in just four steps.

The key to the new process is a protein called amorphadiene synthase, which generates amorphadiene, a key intermediate in the long chain of events that leads to the production of artemisinin. Amorphadiene is then further modified in the plant by reaction with oxygen.

The researchers discovered they could remove several steps of the process by directly using an oxidised precursor of amorphadiene to generate dihydroartemisinic aldehyde, an advanced chemical in the chain of events needed for producing artemisinin.

The development could also be useful in helping to find out why certain patients have shown a resistance to artemisinin, according to Professor Allemann.

He said: "Artemisinin is still the best treatment we have against malaria, and so by creating this new method we hope that researchers will be able to explore this resistance more closely and devise ways of tackling it.

"Our production method is also generic and can be used to create analogues of artemisinin that might allow us to tackle malaria in a number of new ways."

:: The study is published in the chemistry journal Angewandte Chemie.

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