Chemical Properties
Fine-White Crystalline Powder
Description
Artesunate (88495-63-0) is a semisynthetic derivative of the natural product artemisinin which is clinically useful for treatment of malaria and other parasitic diseases. Depolarizes mitochondrial membrane via generation of reactive oxygen species which disrupt the electron transport chain.1?Generation of mitochondrial ROS is dependent on RIP1.2?Inhibits TNFα-induced production of proinflammatory cytokines in human RA fibroblast-like synoviocytes.3?Displays cytotoxicity against a variety of cancer cells4?and cancer stem cells5.
Definition
ChEBI: Artesunate is an artemisinin derivative that is the hemisuccinate ester of the lactol resulting from the reduction of the lactone carbonyl group of artemisinin. It is used, generally as the sodium salt, for the treatment of malaria. It has a role as an antimalarial, a ferroptosis inducer and an antineoplastic agent. It is an artemisinin derivative, a sesquiterpenoid, a dicarboxylic acid monoester, a cyclic acetal, a semisynthetic derivative and a hemisuccinate.
Preparation
Artemisinin was discovered in the 1970s as a result of an extensive screening of Chinese herbal extracts in the search of new antimalarial agents. Currently, the primary method for the production of artemisinin is the isolation from dried leaves of the plant Artemisia annua. Furthermore, the global supply of this life-saving drug exclusively from natural sources remains highly limited. As a result, a novel approaches for large-scale production of artemisinin have been developed. Artesunate is prepared from dihydroartemisinin (DHA) by reacting it with succinic acid anhydride in a basic medium.
A simplified and scalable synthesis of artesunate
Brand name
Arsumax
(Knoll, Switzerland).
General Description
Artesunate is a semisynthetic derivative of artemisinin used to treat malaria. It has also been shown to effective against other parasites such as liver flukes. Artesunate also demonstrates cytotoxic action against cancer cell lines of different tumor types.
Biochem/physiol Actions
Artesunate acts on the electron transport chain, generates local reactive oxygen species, and causes the depolarization of the mitochondrial membrane. It inhibits TNFα-induced production of proinflammatory cytokines via inhibition of NF-κB and PI3 kinase/Akt signal pathway in human rheumatoid arthritis fibroblast-like synoviocytes.
target
NF-kB | p38MAPK | IFN-γ | IL Receptor | PGE | COX | TNF-α | IkB | TGF-β/Smad | gp120/CD4 | Antifection | IKK
Mode of action
Artesunate is a water-soluble, semi-synthetic derivative of the sesquiterpine lactone artemisinin with anti-malarial, anti-schistosomiasis, antiviral, and potential anti-neoplastic activities. It acts on the electron transport chain to generate local reactive oxygen species and cause depolarization of the mitochondrial membrane. It inhibits TNF-induced proinflammatory cytokine production by inhibiting NF-κB and PI3 kinase/Akt signaling pathways in human rheumatoid arthritis fibroblast-like synoviocytes. Artesunate has also been shown to stimulate cell differentiation, arrest the cell cycle in the G1 and G2/M phases, inhibit cell proliferation, and induce apoptosis through mitochondrial and caspase signaling pathways. Artemisinin is isolated from the plant Artemisia annua.
References
1) Li?et al.?(2005),?Yeast model uncovers dual roles of mitochondria in action of artemisinin; PLoS Genet.,?1(3)?e36
2) Chauhan?et al.?(2017),?RIP1-dependent reactive oxygen species production executes artesunate-induced cell death in renal carcinoma Caki cells; Mol. Cell. Biochem.,?435?15
3) Xu?et al. (2007),?Anti-malarial agent artesunate inhibits TNF-alpha-induced production of proinflammatory cytokines via inhibition of NF-kappaB and PI3 kinase/AKt signal pathway in human rheumatoid arthritis fibroblast-like synoviocytes; Rheumatology (Oxford),?46?920
4) Ghantous?et al.?(2010),?What made sesquiterpene lactones reach cancer clinical trials?; Drug. Disc. Today,?15?668
5) Subedi?et al.?(2016),?High-throughput screening identifies artesunate as selective inhibitor of cancer stemness: Involvement of mitochondrial metabolism; Biochem. Biophys. Res. Commun.,?477?737
