109637-83-4Relevant articles and documents
Synthesis of water soluble c-10-phenoxy artemisinin-chitosan conjugate
Xiao, Dan,Yang, Bo,Chen, Yun-Jian,Liao, Xia-Li,Yang, Xue-Min,Qin, Qi-Xue,Yi, Dong
, p. 4654 - 4656 (2013)
A sort of C-10-phenoxy artemisinin-chitosan conjugate, in which C-10-phenoxy artemisinin was covalently bound to chitosan, was prepared and its aqueous solubility was evaluated. The results indicated that the conjugate (1.013 mg/mL) had much higher aqueous solubility than artemisinin (0.0084 mg/mL) and C-10-phenoxy artemisinin (0.0245 mg/mL). The conjugate will be potentially useful for their application as the prodrug of artemisinin.
Synthesis, Antiplasmodial, and Antileukemia Activity of Dihydroartemisinin–HDAC Inhibitor Hybrids as Multitarget Drugs
Bhatia, Sanil,Borkhardt, Arndt,Hansen, Finn K.,Held, Jana,Hogenkamp, Julian,Kraft, Fabian B.,Sch?fer, Thomas Martin,Sch?ler, Andrea,Schliehe-Diecks, Julian,Stopper, Daniel,Tretbar, Maik,von Bredow, Lukas
, (2022/03/27)
Artemisinin-based combination therapies (ACTs) are the gold standard for the treatment of malaria, but the efficacy is threatened by the development of parasite resistance. Histone deacetylase inhibitors (HDACis) are an emerging new class of potential antiplasmodial drugs. In this work, we present the design, synthesis, and biological evaluation of a mini library of dihydroartemisinin–HDACi hybrid molecules. The screening of the hybrid molecules for their activity against selected human HDAC isoforms, asexual blood stage P. falciparum parasites, and a panel of leukemia cell lines delivered important structure–activity relationships. All synthesized compounds demonstrated potent activity against the 3D7 and Dd2 line of P. falciparum with IC50 values in the single-digit nanomolar range. Furthermore, the hybrid (α)-7c displayed improved activity against artemisinin-resistant parasites compared to dihydroartemisinin. The screening of the compounds against five cell lines from different leukemia entities revealed that all hydroxamate-based hybrids (7a–e) and the ortho-aminoanilide 8 exceeded the antiproliferative activity of dihydroartemisinin in four out of five cell lines. Taken together, this series of hybrid molecules represents an excellent starting point toward the development of antimalarial and antileukemia drug leads.
Method and apparatus for the synthesis of dihydroartemisinin and artemisinin derivatives
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, (2015/02/02)
The present invention is directed to a method for continuous production of dihydroartemisinin and also artemisinin derivatives derived from dihydroartemisinin by using artemisinin or dihydroartemisinic acid (DHAA) as starting material as well as to a continuous flow reactor for producing dihydroartemisinin as well as the artemisinin derivatives. It was found that the reduction of artemisinin to dihydroartemisinin in a continuous process requires a special kind of reactor and a special combination of reagents comprising a hydride reducing agent, at least one activator such as an inorganic activator, at least one solid base, at least one aprotic solvent and at least one C1-C5 alcohol.
Effects of highly active novel artemisinin-chloroquinoline hybrid compounds on β-hematin formation, parasite morphology and endocytosis in Plasmodium falciparum
Feng, Tzu-Shean,Guantai, Eric M.,Nell, Margo,Van Rensburg, Constance E.J.,Ncokazi, Kanyile,Egan, Timothy J.,Hoppe, Heinrich C.,Chibale, Kelly
experimental part, p. 236 - 247 (2012/05/05)
4-Aminoquinolines were hybridized with artemisinin and 1,4-naphthoquinone derivatives via the Ugi-four-component condensation reaction, and their biological activities investigated. The artemisinin-containing compounds 6a-c and its salt 6c-citrate were the most active target compounds in the antiplasmodial assays. However, despite the potent in vitro activities, they also displayed cytotoxicity against a mammalian cell-line, and had lower therapeutic indices than chloroquine. Morphological changes in parasites treated with these artemisinin-containing hybrid compounds were similar to those observed after addition of artemisinin. These hybrid compounds appeared to share mechanism(s) of action with both chloroquine and artemisinin: they exhibited potent β-hematin inhibitory activities; they caused an increase in accumulation of hemoglobin within the parasites that was intermediate between the increase observed with artesunate and chloroquine; and they also appeared to inhibit endocytosis as suggested by the decrease in the number of transport vesicles in the parasites. No cross-resistance with chloroquine was observed for these hybrid compounds, despite the fact that they contained the chloroquinoline moiety. The hybridization strategy therefore appeared to be borrowing the best from both classes of antimalarials.
Artemisinin-dipeptidyl vinyl sulfone hybrid molecules: Design, synthesis and preliminary SAR for antiplasmodial activity and falcipain-2 inhibition
Capela, Rita,Oliveira, Rudi,Goncalves, Lidia M.,Domingos, Ana,Gut, Jiri,Rosenthal, Philip J.,Lopes, Francisca,Moreira, Rui
scheme or table, p. 3229 - 3232 (2010/05/02)
A series of artemisinin-vinyl sulfone hybrid molecules with the potential to act in the parasite food vacuole via endoperoxide activation and falcipain inhibition was synthesized and screened for antiplasmodial activity and falcipain-2 inhibition. All conjugates were active against the Plasmodium falciparum W2 strain in the low nanomolar range and those containing the Leu-hPhe core inhibited falcipain-2 in low micromolar range.
Process for one pot conversion of artemisinin into artelinic acid
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Page/Page column title page; 4, (2008/06/13)
The present invention relates to an improved process for one pot conversion of artemisinin into artelinic acid, which reduces the three step (three pot) conversion of artemisinin to artelinic acid in one step (one pot). The process of preparation of artel
A PROCESS FOR ONE POT CONVERSION OF ARTEMISININ INTO ARTELINIC ACID
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Page/Page column 9-10, (2008/06/13)
The present invention relates to an improved process for one pot conversion of artemisinin into artelinic acid, which reduces the three step (three pot) conversion of artemisinin to artelinic acid in one step (one pot). The process of preparation of artel
Sodium artelinate: A potential antimalarial
Shrimali, Meenakshi,Bhattacharya, Asish K.,Jain, Dharam C.,Bhakuni, Rajendra S.,Sharma, Ram P.
, p. 1161 - 1163 (2007/10/03)
An economically viable process is developed for the synthesis of sodium artelinate, a potential antimalarial drug.
Antimalarial Activity of New Water-Soluble Dihydroartemisinin Derivatives
Lin, Ai Jeng,Klayman, Daniel L.,Milhous, Wilbur K.
, p. 2147 - 2150 (2007/10/02)
The usefulness of sodium artesunate (3), a water-soluble derivative of artemisinin (1), is impaired by its poor stability in aqueous solution.To overcome the ease of hydrolysis of the ester group in 3, a new series of derivatives of dihydroartemisinin (2) was prepared in which the solubilizing moiety, which contains a carboxylate group, is joined to dihydroartemisinin by an ether rather than an ester linkage.The new derivatives were prepared in good yield by treatment of dihydroartemisinin with an appropriate alcohol under boron trifluoride etherate catalysis at room temperature.All major condensation products are the β isomer.Hydrolysis of the esters with 2.5percent KOH/MeOH gave the corresponding pottassium salts, which were converted to free acids (8b-d) by acidification.The derivatives were tested in vitro against two clones of human malaria, Plasmodium falciparum D-6 (Sierra Leone clone) and W-2 (Indochina clone).No cross-resistance to the antimalarian agents mefloquine, chloroquine, pyrimethamine, sulfadoxine, and quinine was observed.In general, the new compounds are more effective against the W-2 than the D-6 strain.Esters (5a-d) possess activity comparable to that of the parent compounds 1 and 2; however, conversion of the esters to their corresponding carboxylates (7a-d) or acids (8a-d), with the exception of artelinic acid (8d), drastically decreases the antimalarial activities in both cell lines.Artelinic acid, which is both soluble and stable in 2.5percent K2CO3 solution, possesses superior in vivo activity against Plasmodium berghei than artemisinin or artesunic acid.
