- Synthesis, Evaluation of Anti-Toxoplasma gondii Activity in vitro and Molecular Docking of Dihydroartemisinin Derivatives
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In this work, 21 dihydroartemisinin derivatives were synthesized, their chemical structures were characterized by 1H NMR, 13H NMR and high-resolution MS techniques, and anti-Toxoplasma gondii activity in vitro was evaluated using thiazole blue (MTT) assay. The selectivity index of compound (3R,5aS,6R,8aS,9R,12R,12aR)-3,6,9-trime-thyldeca-hydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl 4-oxo-4-(pyridin-4-ylamino)butanoate (E2) was 2.24, which showed the strongest anti-T. gondii activity. In addition, the results of molecular docking studies show that E2 can be a better inhibitor of T. gondii calcium-dependent protein kinase 1 (TgCDPK1). Therefore, compound E2 has good potential as a drug for T. gondii treatment, and further research is needed to clarify its mechanism of action.
- Chen, Zheng-Ai,Deng, Hao,Quan, Yin-Sheng,Quan, Zhe-Shan,Shen, Qing-Kun
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- Tetravalent platinum complex containing artesunate as well as preparation method and application of tetravalent platinum complex
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The invention discloses a tetravalent platinum complex containing artesunate. The structure of the tetravalent platinum complex is shown as a general formula I or II, wherein R is shown in the specification, and R1 is a branched chain or straight chain saturated C1-C20 alkyl group, or a branched chain or straight chain unsaturated C1-C20 alkyl group. The tetravalent platinum complex containing artesunate provided by the invention has an obvious proliferation inhibition effect on liver cancer HepG2, lung cancer A549, intestinal cancer HCT116, breast cancer MDA-MB-231 and cis-platinum drug-resistant lung cancer, the anti-tumor activity of part of compounds is obviously superior to that of cis-platinum, and the tetravalent platinum complex containing artesunate can be used as anti-tumor candidate drugs for deeper research.
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Paragraph 0045; 0049; 0050
(2021/07/08)
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- Reverse Chemical Proteomics Identifies an Unanticipated Human Target of the Antimalarial Artesunate
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Artemisinins are the most potent and safe antimalarials available. Despite their clinical potential, no human target for the artemisinins is known. The unbiased interrogation of several human cDNA libraries, displayed on bacteriophage T7, revealed a single human target of artesunate; the intrinsically disordered Bcl-2 antagonist of cell death promoter (BAD). We show that artesunate inhibits the phosphorylation of BAD, thereby promoting the formation of the proapoptotic BAD/Bcl-xL complex and the subsequent intrinsic apoptotic cascade involving cytochrome c release, PARP cleavage, caspase activation, and ultimately cell death. This unanticipated role of BAD as a possible drug target of artesunate points to direct clinical exploitation of artemisinins in the Bcl-xL life/death switch and that artesunate's anticancer activity is, at least in part, independent of reactive oxygen species.
- Gotsbacher, Michael P.,Cho, Sung Min,Kim, Nam Hee,Liu, Fei,Kwon, Ho Jeong,Karuso, Peter
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p. 636 - 643
(2019/04/01)
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- Identification of H2S/NO-donating artemisinin derivatives as potential antileukemic agents
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Three H2S/NO-donating artemisinin derivatives were designed and synthesized. Their antiproliferative activities were evaluated against human acute myeloid leukemia (AML) cell lines of K562 and K562/ADR and human normal liver cells of LO2. Biological evaluation indicated that NO-donating compound 10c exhibited the most potent cytotoxicity against leukemia cells, similar to the bioactivity of clinical drug of homoharringtonine, but showed less toxicity than homoharringtonine against LO2 cells. Further mechanism studies revealed that 10c could enhance the levels of intracellular NO and ROS, induce apoptosis and S phase cell cycle arrest, and disturb the mitochondrial membrane potential in K562 and K562/ADR cells. Western blot results demonstrated that 10c noticeably promoted autophagy by up-regulating the levels of Beclin1 and L3-II expression, inhibited the AKT signaling, and stimulated the AMPK and JNK signaling in both leukemia cell lines. Overall, 10c exhibited the potential to be a promising candidate for the therapy of AML.
- Chen, Xuemei,Huang, Pei,Wang, Jing,Tian, Runmei,Chen, Yan,Chen, Yongzheng,Zhang, Lei,Ma, Zhigui
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p. 501 - 511
(2020/01/13)
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- Design and synthesis of novel artemisinin derivatives with potent activities against colorectal cancer in vitro and in vivo
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A series of novel derivatives of artemisinin-4-(arylamino)quinazoline have been designed and synthesized, and most of them showing potent in vitro cytotoxic activity against HCT116 and WM-266-4 cell lines. Compound 32 was the most active derivative against HCT116 cell line with an IC50 of 110 nM, and significantly improved the antitumor activity of the parent compounds dihydroartemisinin (DHA) (IC50 = 2.85 μM) and Gefitinib (IC50 = 19.82 μM). In vivo HCT116 xenografts assay showed that compound 32 exhibited potent antitumor activity with obvious tumor growth delay and tumor shrunken after 18 days treatment on xenografted mice, and especially without loss of body weight. Our results indicate that compounds 32 may represent a safe, novel structural lead for developing new chemotherapy of colorectal cancer.
- Wang, Liang-Liang,Kong, Lingmei,Liu, Hui,Zhang, Yunqin,Zhang, Li,Liu, Xingyong,Yuan, Feng,Li, Yan,Zuo, Zhili
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supporting information
(2019/09/07)
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- Optimized preparation method for artesunate
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The invention discloses an optimized preparation method for artesunate. With dihydroartemisinin and succinic anhydride as raw materials, the artesunate is produced at high yield and high purity through a dropwise adding process and a fine-filtering purification method. The method is simple in process, is low in demand on equipment, is convenient to operate, is high in atom economy, is low-carbon and environment-firendly, and is very suitable for industrial large-scale production. The method has higher advantages in the aspects of economic benefit and environmental protection, and is a creative technology having huge value.
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Paragraph 0030; 0031
(2017/09/01)
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- A simplified and scalable synthesis of artesunate
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Abstract: An efficient and economically viable approach for the large-scale conversion of artemisinin into the antimalarial frontline drug artesunate was developed. This advanced synthesis includes an NaBH4-induced reduction, followed by an esterification with succinic anhydride under basic conditions. The entire conversion follows the principles of green chemistry, i.e., application of reusable solvents. Graphical abstract: [Figure not available: see fulltext.]
- Presser, Armin,Feichtinger, Andrea,Buzzi, Silke
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- Artemisin derivative and its preparation and use
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Provided are artemisinin derivatives of formula (I) or pharmaceutically acceptable salts thereof, or enantiomers, diastereomers, and racemic bodies thereof, and a pharmaceutical composition of the compounds, the preparation process and uses thereof. Artemisinin derivatives of formula (I) have excellent effects in the treatment of tumours.
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Paragraph 0163-0165; 0253-0255
(2016/10/08)
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- Single pot conversion of artemisinin to artesunic acid
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The present invention provides a single pot process for the preparation of artesunic acid from artemisinin involving reduction followed by esterification of the reduced product at room temperature.
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Page column 4
(2008/06/13)
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- SINGLE POT CONVERSION OF ARTEMISININ TO ARTESUNIC ACID
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The present invention provides a single pot process for the preparation of artesunic acid from artemisinin involving reduction followed by esterification of the reduced product at room temperature.
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- C-10 ester and ether derivatives of dihydroartemisinin - 10-α artesunate, preparation of authentic 10-β artesunate, and of other ester and ether derivatives bearing potential aromatic intercalating groups at C-10
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Preparative and stereochemical aspects of reactions providing new C-10 ester and ether derivatives of the antimalarial drug dihydroartemisinin (DHA, 2) have been examined. β-Artesunate has been prepared for the first time, and has been differentiated from the antimalarial α-artesunate; the latter has been incorrectly designated as the β-epimer in Chemical Abstracts and some primary literature. New ester and ether derivatives bearing potential intercalating groups have been synthesised by means of the Schmidt, Mitsunobu and DCC coupling procedures, by acylation in the presence of DMAP, or by hydroxy activation with BF3 as catalyst. When the hydroxy group of DHA acts as a nucleophile towards activated carboxy groups in acylating agents or the DCC intermediate, α-esters are obtained exclusively. When the hydroxy group is activated for displacement by nucleophiles, as in the Schmidt or Mitsunobu procedures, β-esters and β-ethers are obtained either exclusively or predominantly. An exception is represented by the Mitsunobu procedure involving DHA and 1- and 2-naphthols, in which mixtures of epimers are obtained; however, exclusive formation of β-aryl ethers takes place when the Schmidt procedure is used, with activation of the intermediate trichloracetimidate by SnCl2. The latter method is therefore superior to patented procedures for the preparation of β-aryl ethers from nonbasic aryl alcohols without detectable rearrangement to C-aryl compounds. However, the Mitsunobu procedure is better when basic aromatic alcohols are used as nucleophiles. The formation of α-products in which the hydroxy group of DHA acts as a nucleophile is of biological significance in relation to enzyme-mediated Phase II glucuronidation of DHA, in which only the α-DHA glucuronide is formed.
- Haynes, Richard K.,Chan, Ho-Wai,Cheung, Man-Ki,Lam, Wai-Lun,Soo, May-Kei,Tsang, Hing-Wo,Voerste, Arnd,Williams, Ian D.
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p. 113 - 132
(2007/10/03)
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