Artémisinine

The artémisinine (in Chinese: qinghaosu (青蒿素)), is the active ingredient isolated from the annual plant Armoise Artemisia annua (qinghao (青蒿)).

History

The plant, which belongs to the family of the Asteraceae , has been used in Chinese traditional medicine for more than 2000 years. Its presence appears in a formulation going back to 168 av. JC.

The modern history of the artémisinine starts during the Guerre of Vietnam when the North-Vietnamese army builds a whole network of undergrounds. As these tunnels recovered all rainwater, the conveying mosquitos of paludism reproduced in stagnant water. The problem became such extensive, that the North-Vietnamese army lost more soldiers by paludism than by the weapons. The North-Vietnameses then turned to China to try to find a solution.

In 1967, Chinese military researchers thus harnessed themselves to study the traditional remedies containing plants to try to find of them one of effective against the variety of endemic Paludisme in Vietnam. They rather quickly found the armoise annual, in an area of China little touched by this disease. They observed, that with the primary symptom of paludism, the inhabitants of this area drank a decoction of Artemisia annua . This plant had been used in the treatment of a large variety of diseases for more than two millenia. Generally managed in the form of the, it did not have a visible side effect and seemed very effective.

The insulation of the artémisinine, under the direction of the professor Y.Tu, was successful, in 1972 by a researcher trying to extract from it to it (or them) principle (S) active (S). It had the original idea to use a Solvant nonaqueous (Hexane or alcohol according to the versions). It obtained (after purifications repeated on Silica gel) a yellowish oily substance which it could crystallize in a powder blanchâtre slightly water soluble but well in the majority of organic solvents (Dichlorométhane, Acétone) having a good thermal stability to room temperature and, most important, able to kill P. falciparum in vitro . Its antipaludic actions (discoveries by the Chinese doctor naturalist and pharmacologist, Li Shizhen) and the development of a simple process of extraction quickly followed.

Its structure was confirmed in 1979 by crystallographic analyzes by x-rays and by using a Electron microscope with sweeping. It is a sesquiterpenic Lactone with two atoms of Oxygène bound by a bridge Peroxyde above a cycle to seven atoms of Carbone (cf the table on the right). With nine centers of asymmetry authorizing a great number of Stéréoisomère S it is a chance that Artemisia annua synthesizes one of them; nevertheless, the completely asymmetrical character of the molecule of artémisinine makes its synthesis artificial particularly difficult, in particular at acceptable cost (from where the use of semi-synthetic derivatives like the Artésunate, the Artéméther and the Artéether).

It is only after the aggravation of the phenomena of resistance of the parasite towards the traditional drugs like the Chloroquine, the Amodiaquine… at the beginning of the Années 1990 that the pharmaceutical laboratories started to be interested in it, and it had to be waited until 2001 so that WHO declares the artémisinine “the greatest hope world against paludism”; in 2006, it recommended however to stop the Monothérapie in order to avoid the risks of resistance: the artémisinine weakens the parasite but does not kill it systematically, and it has its maximum effectiveness in partnership with the other anti-paludic ones (ACT).

Operation

The artémisinine is a sesquiterpenic lactone carrying a group peroxidizes which seems to be the key of its effectiveness. It would block an enzyme which makes it possible the parasite to pump calcium thus preventing it from developing.

While the artéméther, the reduced peroxide molecule of the artémisinine, reacts with the iron of the red globules to create free radicals which, in their turn, destroy the membranes of the parasite or out of the cancer cell and kill them. To note however that the presence of any substance protecting from the ridicalizing damage (Antioxydant) could oppose its effectiveness.

Treatment of the malaria

Treatment of cancer

Treatment of schistosomiasis

See too

References

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