Artemether Lumefantrine Coartem

Structural Formula h3c

Ball-and-Stick Model

Space-filling Model h3c

Structural Formula Coartem

= Carbon = Hydrogen = Oxygen

Space-filling Model

= Carbon = Hydrogen = Oxygen

Year of discovery: 1971 (Shanghai Institute of Materia Medica); Year of introduction: 1998; Drug category: Trioxane antimalarial; Main uses: For the treatment of uncomplicated and severe malaria (Plasmodium falciparum) in mono and combination therapies, especially in cases of resistant strains; Related drugs: Dihydroartemisinin, Artemether, Arteether, Artesunate, Mefloquine + Artesunate (Artequin), Amodiaquine + Artesunate (ASAQ, Coarsucam).

Artemisinin, a complex natural product, and its derivatives such as dihydroartemisinin, artemether, arteether and sodium artesunate are potent, fast-acting and widely used antimalarial drugs (see structures below).

longer-acting antimalarial drugs lumefantrine and mefloquine.

such as

Arteether

Arteether

Artemisinin was first isolated in 1971 from the Chinese medicinal herb Artemisia annua, in which it is the main constituent.1 The herb has been used in China to reduce fever for over a millenium. Once the potent antimalarial activity of artemisinin had been established, several analogs were prepared to improve bioavailability and efficacy, including sodium artesunate which serves as a water-soluble prodrug.

The optimum therapy for malaria depends on several factors including severity of illness, patient age and history and likelihood of resistance to a first-line drug. The recommended standard treatment of uncomplicated malaria involves the oral administration of artemisinin derivatives in combination with

Lumefantrine cf3

Mefloquine

Lumefantrine cf3

Mefloquine

The combination of lumefantrine and artemether is highly effective and well-tolerated as an oral antimalarial drug (Coartemâ„¢, Novartis) with cure rates above 95%. Artemisinin is produced in China on a large scale by extraction of the dry Artemisia annua plant. Increased worldwide demand (>120 million doses) for Coartem led to the establishment of plantations and extraction facilities in Africa as well.

Artemisinins have high efficacy against Plasmodium falciparum in the blood stages of the disease. Their mode of action has not been proven, but the endoperoxide (O-O) subunit of the trioxane ring is critical for antimalarial activity. The 0-0 bond is easily broken by transfer of an electron from FeiT species, generating a number of reactive intermediates such as oxygen- and carbon-centered radicals that oxidatively damage the parasite/ It may also be relevant that artemisinins strongly inhibit the Ca2+-ATPase in the endoplasmatic reticulum of the parasite that is needed for the maintenance of optimal calcium levels.3

1. Med. Chem. Bioact. Nat. Prod. 2006, 183-256; 2. Acc. Chem. Res 2004, 37, 397-404; 3. Int. J. Parasitol. 2006, 36, 1427-1441; Refs. p. 179

Artemisinin

Dihydroartemisinin o

Sodium artesunate

Artemisinin

Dihydroartemisinin o

Sodium artesunate

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