101020-89-7Relevant academic research and scientific papers
Novel spirobicyclic artemisinin analogues (artemalogues): Synthesis and antitumor activities
Liu, Gang,Song, Shanshan,Shu, Shiqi,Miao, Zehong,Zhang, Ao,Ding, Chunyong
, p. 17 - 28 (2015)
The sesquiterpene lactone framework of artemisinin was used as a drug repositioning prototype for the development of novel antitumor drugs. Several series of novel artemisinin analogues (artemalogues) were designed and synthesized through 1,3-dipolar cycloaddition of artemisitene with nitrile oxides or nitrones. The isoxazolidine-containing spirobicyclic artemalogue 11b turns out to be the most potent with low micromolar IC50 values against all three tumor cells, which were at least 4-to 14-fold more potent than the parent artemisinin.
Correlation of antimalarial activity of artemisinin derivatives with binding affinity with ferroprotoporphyrin IX
Paitayatat, Sumpan,Tarnchompoo, Bongkoch,Thebtaranonth, Yodhathai,Yuthavong, Yongyuth
, p. 633 - 638 (1997)
The antimalarial activity of a number of artemisinin derivatives, both newly synthesized and currently used as drugs, against Plasmodium falciparum in culture shows a correlation with their affinity of binding with ferroprotoporphyrin IX, as measured from the spectral change of the latter. The new C-16-functionalized artemisinin derivatives were obtained through a novel one-pot synthesis of artemisitene (2) from naturally abundant artemisinin (1), followed by Michael addition with nucleophiles. The correlation points to the biological significance of the interaction of these derivatives with ferroprotoporphyrin IX and may provide a basis for primary screening of peroxidic antimalarials of similar structures.
Anti-proliferative and anti-malarial activities of spiroisoxazoline analogues of artemisinin
Pratap, Surya,Naaz, Fatima,Reddy, Srinivas,Jha, Kunal K.,Sharma, Kalicharan,Sahal, Dinakar,Akhter, Mymoona,Nayakanti, Devanna,Kumar, Halmuthur M. S.,Vandana,Pandey, Kailash,Shafi, Syed
, (2019)
A series of spiroisoxazoline analogues of artemisinin was synthesized by employing 1,3-dipolar cycloaddition between various in situ generated nitrile oxides and artemisitene. All the synthesized compounds were tested for their anti-proliferative and anti
Combination of Pseudo-Natural Product Design and Formal Natural Product Ring Distortion Yields Stereochemically and Biologically Diverse Pseudo-Sesquiterpenoid Alkaloids
Liu, Jie,Flegel, Jana,Otte, Felix,Pahl, Axel,Sievers, Sonja,Strohmann, Carsten,Waldmann, Herbert
supporting information, p. 21384 - 21395 (2021/08/23)
We describe the synthesis and biological evaluation of a new natural product-inspired compound class obtained by combining the conceptually complementary pseudo-natural product (pseudo-NP) design strategy and a formal adaptation of the complexity-to-diversity ring distortion approach. Fragment-sized α-methylene-sesquiterpene lactones, whose scaffolds can formally be viewed as related to each other or are obtained by ring distortion, were combined with alkaloid-derived pyrrolidine fragments by means of highly selective stereocomplementary 1,3-dipolar cycloaddition reactions. The resulting pseudo-sesquiterpenoid alkaloids were found to be both chemically and biologically diverse, and their biological performance distinctly depends on both the structure of the sesquiterpene lactone-derived scaffolds and the stereochemistry of the pyrrolidine fragment. Biological investigation of the compound collection led to the discovery of a novel chemotype inhibiting Hedgehog-dependent osteoblast differentiation.
[...] and Isoxazolidine substituted artemisinin derivatives, preparation method and application thereof (by machine translation)
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Paragraph 0160, (2017/07/20)
The invention provides a [...] and Isoxazolidine substituted artemisinin derivatives, its preparation method and application, in particular, the invention provides a compound of formula I is shown. Wherein the definition of each group as described in the
Artemisone - A highly active antimalarial drug of the artemisinin class
Haynes, Richard K.,Fugmann, Burkhard,Stetter, Joerg,Rieckmann, Karl,Heilmann, Hans-Dietrich,Chan, Ho-Wai,Cheung, Man-Ki,Lam, Wai-Lun,Wong, Ho-Ning,Croft, Simon L.,Vivas, Livia,Rattray, Lauren,Stewart, Lindsay,Peters, Wallace,Robinson, Brian L.,Edstein, Michael D.,Kotecka, Barbara,Kyle, Dennis E.,Beckermann, Bernhard,Gerisch, Michael,Radtke, Martin,Schmuck, Gabriele,Steinke, Wolfram,Wollborn, Ute,Schmeer, Karl,Roemer, Axel
, p. 2082 - 2088 (2007/10/03)
Artemisinin - the next generation: Efficacies of artemisone against the malaria parasite are substantially greater than those of the current artemisinin "gold standard", artesunate. Also, in contrast to most current artemisinins it displays low lipophilic
ARTEMISININ-BASED PEROXIDE COMPOUNDS AS BROAD SPECTRUM ANTI-INFECTIVE AGENTS
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Page/Page column 44, (2010/02/07)
Described herein is the synthesis, bioassay results and utility of new C-9 and C-10 substituted artemisinin derivatives with easily functionalizable groups attached to the artemisinin skeleton through carbon chain or heteroatoms. Described also is the demonstration of this class of compounds for their broad-spectrum anti-parasitic activity. Certain of these analogs possess noticeable cytotoxicity deliberately focused on treatment of cancerous diseases.
Structure-activity relationships of the antimalarial agent artemisinin. 8. Design, synthesis, and CoMFA studies toward the development of artemisinin-based drugs against leishmaniasis and malaria
Avery, Mitchell A.,Muraleedharan, Kannoth M.,Desai, Prashant V.,Bandyopadhyaya, Achintya K.,Furtado, Marise M.,Tekwani, Babu L.
, p. 4244 - 4258 (2007/10/03)
Artemisinin (1) and its analogues have been well studied for their antimalarial activity. Here we present the antimalarial activity of some novel C-9-modified artemisinin analogues synthesized using artemisitene as the key intermediate. Further, antileish
Structure-activity relationships of the antimalarial agent artemisinin. 7. Direct modification of (+)-artemisinin and in vivo antimalarial screening of new, potential preclinical antimalarial candidates
Avery, Mitchell A.,Alvim-Gaston, Maria,Vroman, Jeffrey A.,Wu, Baogen,Ager, Arba,Peters, Wallace,Robinson, Brian L.,Charman, William
, p. 4321 - 4335 (2007/10/03)
On the basis of earlier reported quantitative structure-activity relationship studies, a series of 9β-16-(arylalkyl)-10-deoxoartemisinins were proposed for synthesis. Several of the new compounds 7 and 10-14 were synthesized employing the key synthetic intermediate 23. In a second approach, the natural product (+)-artemisinic acid was utilized as an acceptor for conjugate addition, and the resultant homologated acids were subjected to singlet oxygenation and acid treatment to provide artemisinin analogues. Under a new approach, we developed a one step reaction for the interconversion of artemisinin 1 into artemisitene 22 that did not employ selenium-based reagents and found that 2-arylethyliodides would undergo facile radical-induced conjugate addition to the exomethylene lactone of 22 in good yield. The lactone carbonyls were removed sequentially by diisobutylaluminum hydride reduction followed directly by a second reduction (BF3-etherate/Et3SiH) to afford the desired corresponding pyrans. Six additional halogen-substituted aromatic side chains were installed via 22 furnishing the bioassay candidates 15-20. The analogues were examined for in vitro antimalarial activity in the W-2 and D-6 clones of Plasmodium falciparum and were additionally tested in vivo in Plasmodium berghei- and/or Plasmodium yoelii-infected mice. Several of the compounds emerged as highly potent orally active candidates without obvious toxicity. Of these, two were chosen for pharmacokinetic evaluation, 14 and 17.
Synthesis of 6,7-dehydroartemisinic acid
Sy,Brown
, p. 2421 - 2429 (2007/10/03)
The natural product 6,7-dehydroartemisinic acid from Artemisia annua has been synthesized in four steps from artemisitene, which was in turn prepared in four steps from commercially available artemisinin. The forward synthesis involves the acid degradation of artemisitene and some comparisons are made between the products from this reaction and the more extensively studied acid degradation reaction of its 11,13-dihydro analogue, artemisinin.
