216963-48-3Relevant academic research and scientific papers
Effects of artemisinin-tagged holotransferrin on cancer cells
Lai, Henry,Sasaki, Tomikazu,Singh, Narendra P.,Messay, Archna
, p. 1267 - 1279 (2005)
Artemisinin reacts with iron to form free radicals that kill cells. Since cancer cells uptake relatively large amount of iron than normal cells, they are more susceptible to the toxic effect of artemisinin. In previous research, we have shown that artemisinin is more toxic to cancer cells than to normal cells. In the present research, we covalently attached artemisinin to the iron-carrying plasma glycoprotein transferrin. Transferrin is transported into cells via receptor-mediated endocytosis and cancer cells express significantly more transferrin receptors on their cell surface and endocytose more transferrin than normal cells. Thus, we hypothesize that by tagging artemisinin to transferrin, both iron and artemisinin would be transported into cancer cells in one package. Once inside a cell, iron is released and can readily react with artemisinin close by tagged to the transferrin. This would enhance the toxicity and selectivity of artemisinin towards cancer cells. In this paper, we describe a method to synthesize such a compound in which transferrin was conjugated with an analog of artemisinin artelinic acid via the N-glycoside chains on the C-domain. The resulting conjugate ('tagged-compound') was characterized by MALDI-MS, UV/Vis spectroscopy, chemiluminescence, and HPLC. We then tested the compound on a human leukemia cell line (Molt-4) and normal human lymphocytes. We found that holotransferrin-tagged artemisinin, when compared with artemisinin, was very potent and selective in killing cancer cells. Thus, this 'tagged-compound' could potentially be developed into an effective chemotherapeutic agent for cancer treatment.
Process for one pot conversion of artemisinin into artelinic acid
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Page/Page column title page; 4-5, (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
An improved procedure for the synthesis of ethers of dihydroartemisinin
Bhakuni, Rajendra S.,Jain, Dharam C.,Sharma, Ram P.
, p. 529 - 530 (2007/10/02)
A simple and efficient method for the preparation of ethers (3a-f) of dihydroartemisinin (2) has been developed using chlorotrimethylsilane as a catalyst.
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.
