ARTEMOTIL (PhEur)

Artemotil (CAS – 75887-54 beta-arteether) is an antimalarial artemisinin derivative, approved for the treatment of severe cases of P. falciparum malaria. The mixture of artemotil and alpha-arteether is used in patients with cerebral malaria. Most of the artemisinin compounds including artemotil are metabolized into dihydroartemisinin, which is responsible for antimalarial activity. These compounds contain stable endoperoxide bridge. The antimalarial activity of the drug thus is dependent on the cleavage of the endoperoxide by intraparasitic heme. The cleaved endoperoxide ultimately becomes a carbon centered free radical, which then functions as an alkylating agent, reacting with both heme and parasitic proteins (but not DNA). In P. falciparum, one of the principal alkylation target is the translationally controlled tumor protein (DHA-TCTP) homolog. Some intraparasitic TCTP is situated in the membrane surrounding the heme-rich food vacuole, where heme could catalyse the formation of drug-protein (DHA-TCTP)