artesunate brands

Molecular formula: C19H28O8

Artesunate is metabolized to the active DHA. the endoperoxide bridge of DHA reacts with heme, generating free radicals which inhibit protein and nucleic acid synthesis of the _Plasmodium_ parasites during all erythrocytic stages. Reactions with these free radicals can also lead to alkylation of parasitic proteins such as a calcium adenosine triphosphatase and EXP1, a glutathione S-transferase. Two theories have been put forward for the mode of antimalarial action of the artemisinin antimalarials, in accodance with the known properties of peroxides with medicinal activity. The first assumes that the artemisinins must be activated by contact with either reduced haem (ferrous haem, Fe(ll)PPIX) or non-haem ferrous iron (exogenous iron), causing cleavage of the peroxide to generate oxygen-centered radicals (alkoxy radicals') which are the presumed to be converted into carbon-centered radicals by transfer of proximate hydrogen atoms from the periphery of the peroxide molecule. These carbon-centered radicals are then thought to alkylate sensitive, yet unspecified, biomolecules in the parasite. A second theory argues for a process in which the intact artemisinin binds to a site within a vital protein in the parasite. The act of binding causes the peroxide to be converted to hydroperoxide or similar open peroxide, which in accordance with known properties of such compounds, generates one or more active chemical entities, either oxidizing agents or oxygen transfer agents per se, or oxygen-centered free radicals. This would be associated with the binding process. In such a way, the artemisinins might act as (irreversibile) inhibitors. Iron may, or may not, be associated with the activation process. No specific biological target in the parasite has yet been identified in support of this theory, but it may be membrane-bound proteins. Artesunate is a water soluble derivative of artemisinin, an antimalarial compound isolated from the Chinese herb Qinghao (Artemisia annua). Artesunate is rapidly metabolized to dihydroartemisinin (DHA) in the body. Chemically, artesunate, and its active metabolite, DHA, are sesquiterpene lactones with a trioxane ring containing a peroxide bridge. The peroxide bridge appears to be essential for the antimalarial activity of artesunate. Structure-activity relationship studies show that the deoxy derivative of DHA (that lack the peroxide bridge) was 277-fold less active than DHA. The activity of deoxyartesunate was not measured. Deoxy derivatives of other artemisinin analogs were 10- to 1000-fold less active compared to the parent compounds. Artesunate increases superoxide anion production and lipid peroxidation in falciparum-infected erythrocytes in vitro. However, artesunate does not suppress the activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase) in infected or uninfected erythrocytes. Erythrocytes infected with the ring or trophozoite forms in vitro accumulate 100- and 180- fold higher concentrations of DHA (12 nM ie, 3.40 ng/mL), respectively, compared to uninfected erythrocytes. These experiments were performed in a medium containing 10% human serum. The relevance of these findings to the uptake in vivo is unclear. The precise mechanism by which artesunate exhibits antiplasmodial activity is not understood. A 2025 systematic review notes Artesunate's pharmacological activities (antimalarial, antiparasite,antitumor, antivirus, antiinflammation, and antibacterial),and that it is a highly effective antimalarial agent with the potential to induce organ toxicity under certain conditions. The authors note that mechanisms of Artesunate-induced toxicity include oxidative stress, inflammation, and apoptotic signaling patthhways.They also note that Artesunate ameliorates MASH (Metabolic Dysfunction-Associated Steatohepatitis) by reducing inflammation and lipid accumulation by regulating NLRP3 inflammasome and reducing lipid accumulation (SREBP-1c, FAS).

Source: PubChem (NCBI) · compound 6917864