81496-81-3Relevant articles and documents
Development and validation of a liquid chromatography and ion spray tandem mass spectrometry method for the quantification of artesunate, artemether and their major metabolites dihydroartemisinin and dihydroartemisinin-glucuronide in sheep plasma
Duthaler, Urs,Keiser, Jennifer,Huwyler, Joerg
, p. 172 - 181 (2011)
Recently, promising fasciocidal activities of artesunate and artemether were described in rats and sheep. Therefore, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to quantify artesunate, artemether and their metabolites dihydroartemisinin and dihydroartemisinin-glucuronide in sheep plasma. Protein precipitation with methanol was used for sample workup. Reversed-phase high-performance liquid chromatography (HPLC) was performed using an Atlantis C18 analytical column with a mobile phase gradient system of ammonium formate and acetonitrile. The analytes were detected by MS/MS using selected reaction monitoring (SRM) with electrospray ionisation in the positive mode (transition m/z 267.4 → 163.0). The analytical range for dihydroartemisinin, dihydroartemisinin-glucuronide and artesunate was 10-1000 ng/ml and for artemether 90-3000 ng/ml with a lower limit of quantification of 10 and 90 ng/ml, respectively. Inter- and intra-day accuracy and precision deviations were 10%. Consistent relative recoveries (60-80%) were observed over the investigated calibration range for all analytes. All analytes were stable in the autosampler for at least 30 h (6 °C) and after three freeze and thaw cycles. The validation results demonstrated that the LC-MS/MS method is precise, accurate and selective and can be used for the determination of the artemisinins in sheep plasma. The method was applied successfully to determine the pharmacokinetic parameters of artesunate and its metabolites in plasma of intramuscularly treated sheep.
Second generation, orally active, antimalarial, artemisinin-derived trioxane dimers with high stability, efficacy, and anticancer activity
Paik, Ik-Hyeon,Xie, Suji,Shapiro, Theresa A.,Labonte, Tanzina,Narducci Sarjeant, Amy A.,Baege, Astrid C.,Posner, Gary H.
, p. 2731 - 2734 (2006)
In only two steps and in 63% overall yield, naturally occurring 1,2,4-trioxane artemisinin (1) was converted into C-10-carba trioxane conjugated diene dimer 4. This new dimer was then transformed easily in one additional 4 + 2-cycloaddition step into phthalate dimer 5, and further modification led to bis-benzyl alcohol dimer 7 and its phosphorylated analogues 8 and 9. Bis-benzyl alcohol dimer 7 is the most antimalarially active in vitro, 10 times more potent than artemisinin (1). Bis-benzyl alcohol dimer 7 is approximately 1.5 times more orally efficacious in rodents than the antimalarial drug sodium artesunate and is about 37 times more efficacious than sodium artesunate via subcutaneous administration. Both dimers 5 and 7 are thermally stable neat even at 60 °C for 24 h. Phthalate dimer 5 is very highly growth inhibitory but not cytotoxic toward several human cancer cell lines; both dimers 5 and 7 very efficiently and selectively kill human cervical cancer cells in vitro in a dose-dependent manner with no cytotoxic effects on normal cervical cells.
Synthesis and cytotoxicity studies of artemisinin derivatives containing lipophilic alkyl carbon chains
Liu, Yungen,Wong, Vincent Kam-Wai,Ko, Ben Chi-Bun,Wong, Man-Kin,Che, Chi-Ming
, p. 1561 - 1564 (2005)
(Chemical Equation Presented) Cytotoxic artemisinin derivatives have been synthesized by a modular approach of "artemisinin + linker + lipophilic alkyl carbon chain". A strong correlation between the length of the carbon chains and the cytotoxicities against human hepatocellular carcinoma (HepG2) was revealed. Notably, compared with artemisinin (IC50 = 97 μM), up to 200-fold more potent cytotoxicity (IC50 = 0.46 μM) could be achieved by attachment of a C14H29 carbon chain to artemisinin via an amide linker.
A novel artemisinin-quinine hybrid with potent antimalarial activity
Walsh, John J.,Coughlan, David,Heneghan, Nicola,Gaynor, Caroline,Bell, Angus
, p. 3599 - 3602 (2007)
Artemisinin was reduced to dihydroartemisinin and coupled to a carboxylic acid derivative of quinine via an ester linkage. This novel hybrid molecule had potent activity against the 3D7 and (drug-resistant) FcB1 strains of Plasmodium falciparum in culture. The activity was superior to that of artemisinin alone, quinine alone, or a 1:1 mixture of artemisinin and quinine.
Method for preparing dihydroartemisinin crude drug by single process
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Paragraph 0046-0088, (2019/08/03)
The invention belongs to the technical field of production of dihydroartemisinin crude drugs, and particularly relates to a method for preparing a dihydroartemisinin crude drug through a single process. The method comprises the following steps: S1, dissolving artemisinin in a non-protonic solvent; S2, sequentially adding a phase transfer catalyst and a reducing agent, and performing reduction reaction on the artemisinin; S3, adjusting the pH value of the reaction system obtained in step the S2 to 5-7 with acid liquor, adding water, stirring, performing liquid separating, extracting a water phase obtained by the liquid separating with the same non-protonic solvent as in the step S1, and finally combining an organic phase obtained by the extracting with an organic phase obtained by liquid separating, washing with water, and drying; and S4, precipitating crystals from the dried organic phase obtained by the S3 in a crystallization-filter pressing-drying three-in-one crystallization device, then concentrating, filter-pressing and drying to obtain a dihydroartemisinin refined product. The invention provides the method for preparing the high-purity dihydroartemisinin crude drug, and thepurity and the yield of the dihydroartemisinin prepared by the method can reach more than 99%.
Artemisinin-indole and artemisinin-imidazole hybrids: Synthesis, cytotoxic evaluation and reversal effects on multidrug resistance in MCF-7/ADR cells
Hu, Yanping,Li, Na,Zhang, Jiayao,Wang, Ying,Chen, Li,Sun, Jianbo
, p. 1138 - 1142 (2019/03/04)
A series of artemisinin derivatives with MDR reversal activity were designed and synthesized. All hybrids were screened to anticancer activities against four human cancer cell lines (A549, MCF-7, HepG-2, MDA-MB-231) and normal human hepatic cell (L02) in vitro. Most of the new compounds showed higher anticancer activities than artemisinin, among which compounds 11a and 11c displayed superior potency with IC50 6.78 μM and 5.25 μM against MCF-7, respectively. The further research indicated that the most potent 11c induced cell cycle arrest at G2 phase in MCF-7. Additionally, compound 11c showed remarkable MDR reversal activity which reversed adriamycin against MCF-7/ADR cells with IC50 0.76 μM.
A process for preparing β - pedic ether process
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Paragraph 0029-0030, (2018/04/21)
The invention discloses a technology for preparing beta-artemether. The technology comprises the following steps: reducing an initial raw material artemisinin in the presence of a reducing agent to generate dihydroartemisinin, and carrying out an etherification reaction on dihydroartemisinin and trimethyl orthoacetate in the presence of a catalyst to prepare beta-artemether. Experiments prove that the technology allows the content of alpha-artemether generated in the methyl etherification reaction to be smaller than 3%, the HPLC purity of the obtained beta-artemether to be improved to above 99.8%, the content of single impurities to be smaller than 0.1% respectively and the quality of the above product to accord with requirements of United States Pharmacopeia; and the total mole yield of the product by artemisinin can reach 95% or above. The technology can avoid tedious intermediate processing links in the prior art, realizes simple-operation low-cost high-yield preparation of highly pure beta-artemether, accords with industrial production demands of beta-artemether, and has industrial application values.
Design, synthesis, and antiplasmodial activity of hybrid compounds based on (2 R,3 S)- N-benzoyl-3-phenylisoserine
Njogu, Peter M.,Gut, Jiri,Rosenthal, Philip J.,Chibale, Kelly
supporting information, p. 637 - 641 (2013/07/26)
A series of hybrid compounds based on (2R,3S)-N-benzoyl-3-phenylisoserine, artemisinin, and quinoline moieties was synthesized and tested for in vitro antiplasmodial activity against erythrocytic stages of K1 and W2 strains of Plasmodium falciparum. Two hybrid compounds incorporating (2R,3S)-N-benzoyl-3- phenylisoserine and artemisinin scaffolds were 3- to 4-fold more active than dihydroartemisinin, with nanomolar IC50 values against Plasmodium falciparum K1 strain.
New method for the synthesis of ether derivatives of artemisinin
Bora, Pranjal P.,Baruah, Nabajyoti,Bez, Ghanashyam,Barua, Nabin C.
body text, p. 1218 - 1225 (2012/04/04)
Dihydroartemisinin can be converted to its ether derivatives in good yields by reaction with different alcohols in the presence of a catalytic amount of dodecatungstophosphoric acid hydrate. Easy handling, trouble-free workup by filtration, excellent yields, and very short reaction times are some of the highlights of this protocol. Copyright Taylor & Francis Group, LLC.
Facile stoichiometric reductions in flow: An example of artemisinin
Fan, Xiaolei,Sans, Victor,Yaseneva, Polina,Plaza, Dorota D.,Williams, Jonathan,Lapkin, Alexei
experimental part, p. 1039 - 1042 (2012/08/07)
Stoichiometric reduction of artemisinin to dihydroartemisinin (DHA) has been successfully transferred from batch to continuous flow conditions with a significant increase in productivity and an increase in selectivity. The DHA space-time-yield of up to 1.6 kg h-1 L-1 was attained which represents a 42 times increase in throughput compared to that of conventional batch process.
