Artemisinin is a drug used to treat multi-drug resistant strains of falciparum
malaria. The compound (a sesquiterpene lactone) is isolated from the shrub Artemisia annua. Not all shrubs of this species contain artemisinin.
Apparently it is only produced when the plant is subjected to certain conditions.
Chemically it is
(3R,5aS,6R,8aS,9R,12S,12aR)-octahydro-3,6,9-trimethyl-3,12-epoxy-12H-pyrano[4,3-
j]-1,2-benzodioxepin-10(3H)-one, C15H22O5.
History
Artemisia has been used by Chinese herbalists for more than a thousand years in the treatment of many illnesses, such
as skin diseases and malaria. In the 1960s a research program was set up by the Chinese army to find an adequate treatment of
malaria. In 1972, in the course of this research, Tu Youyou discovered artemsinin in the leaves of Artemisia annua. The drug is named qinghaosu in Chinese. It was one of many candidates then tested
by Chinese scientists from a list of nearly 200 traditional Chinese
medicines for treating malaria. It was the only one that was effective.
It remained largely unknown to the rest of the world for about 10 years, due to the Communist Chinese government at the time.
The rest of the world finally found out about the drug from an article in a Chinese medical journal. People were sceptical at
first, because the Chinese had made unsubstantiated statements about having found treatments of malaria before. Another reason
was the peroxide part of the molecule. It was thought unlikely this would be a stable molecule, and so would not last long enough
to be effective. This turned out not to be the case.
The Chinese government at the time, however, was very wary of western scientists, and would not give anyone either the plant
or the refined drug. People around the world now started looking for the shrub themselves, to see if they could find it. They
finally found it along the Potomac river, in Washington, D.C. Apparently it was a very common shrub, found in many
parts of the world. It took another 10 years of research before the drug finally became commercially available. By this time
relations between Communist China and the rest of the world had improved, and scientific information could be exchanged.
The drug is used these days in China and Vietnam without much regard to taking precautions against creating resistance of the
malaria parasite to this drug as well.
More potent derivatives have also been developed from artemisinin, such as
artemether and artesunate. However, their activity decreases after one to two hours. To counter this drawback,
artemisinin is given alongside lumefantrine to treat uncomplicated falciparum malaria. Lumefantrine has a half-life of about 3 to 6 days.
Such a treatment is called ACT (artemisinin-based combination
therapy); other examples are artemether-lumefantrine, artesunate-mefloquine, artesunate-amodiaquine, and artesunate-sulfadoxine/pyrimethamine.
Recent trials have shown that ACT is more than 90% effective, with a recovery of malaria after three days, especially for the
chloroquine-resistant Plasmodium falciparum.
The World Health Organisation has recommended
that a switch to ACT should be made in all countries were the malaria parasite has developed resistance to chloroquine. Artemisinin and its derivitives are now standard components of malaria
treatment in China, Vietnam, and some other countries in Asia and Africa, where they have proved to be the best-ever
anti-malarial drugs. They have minimal adverse side effects. Currently, artemisinin is not widely available in the United States
or Canada.
To counter the present shortage in leaves of Artemisia annua, researchers have been searching for a way to develop
artemisinin artificially in the laboratory. The compound, called OZ-277, developed by Jonathan Vennerstrom in University of Nebraska has even proved to be more effective
than the natural product in test-tube trials.
How it works
The compound has a peroxide group in its structure. When the
peroxide comes into contact with high iron concentrations, the molecule becomes unstable
and "explodes" into free radicals. High concentrations of iron are found in red blood cells, which is also where the malaria parasites are found. When the compound enters the red blood
cell, it will release the free radicals, which are highly destructive to the parasites.
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