Stereochemistry-Dependent Cytotoxicity of Some Artemisinin Derivatives

Abstract

We determined the cytotoxicity of some artemisinin derivatives against EN2 tumor cells using the MTT assay. Artemisinin (1) was clearly more cytotoxic than deoxyartemisinin (2), which lacks the endoperoxide bridge. Ether-linked dimers of dihydroartemisinin with defined stereochemistry were found to differ in the extent of cytotoxic effect on EN2 cells. The nonsymmetrical dimer (3) was more cytotoxic than the symmetrical dimer (4). The nonsymmetrical dimer of dihydrodeoxyartemisinin (5) lacking the endoperoxide bridges was also effective in the MTT assay, although less cytotoxic than 3 and 4. Similarly, the symmetrical dimer (6) was less effective than 5. Epoxides of artemisitene also showed that stereochemistry was an important factor for cytotoxicity. The results suggested that the endoperoxide bridge was not crucial for cytotoxicity to the tumor cells, but contributed to the cytotoxic effect apparently exerted by the ether linkage of the dimers. Flow cytometry data indicated that the dimers 3 and 4 caused an accumulation of the cells in the G1-phase of the cell cycle. In contrast, artemisinin (1) caused a slight increase of S-phase cells.

In vitro Antiproliferative Activity of Endemic Centaurea kilaea Boiss. against Human Tumor Cell Lines

“…Cytotoxicity testing in vitro was done by the method of modified Woerdenbag et al (15,16). The MTT metabolic assay was carried out in seeded at the density of 1x10 4 cells/ well in 96-well flat-bottom cell culture plates with 100 μL of opti-MEM and 24-48 hours incubation at 37ºC, 5% CO 2 ..…”

Synthesis and evaluation of cytotoxic activities of some substituted isoxazolone derivatives

“…Cell viability and cytotoxic activity profile of the compounds were analyzed using the MTT assay (29,30,31). MTT is cleaved to formazan by the "succinate-tetrazolium reductase" system (EC 1.3.99.1) which belongs to the mitochondrial respiratory chain and is active only in viable cells.…”

“…Cytotoxicity testing in vitro was done by the method of modified Woerdenbag et al (30,31). The MTT metabolic assay was carried out in seeded at the density of 1x10 4 cells/well in 96-well flat-bottom cell culture plates well plates with 200 μL of opti-MEM (invitrogen, USA) and incubated for 24 hours at 37ºC, 5% CO 2.…”

Synthesis and Anticancer Activity of Novel Deoxoartemisinin–Glycolipid Hybrids

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