Synthesis, antimalarial activity and cytotoxicity of 10-aminoethylether derivatives of artemisinin
Date
2012Author
Cloete, Theunis T.
Breytenbach, J. Wilma
Breytenbach, Jaco C.
N'Da, David D.
De Kock, Carmen
Smith, Peter J.
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In this study, a series of 11 10-aminoethylether derivatives of artemisinin were synthesised and their
antimalarial activity against both the chloroquine sensitive (D10) and resistant (Dd2) strains of Plasmodium
falciparum was determined. The compounds were prepared by introducing aliphatic, alicyclic and
aromatic amine groups with linkers of various chain lengths through an ethyl ether bridge at C-10 of
artemisinin using conventional and microwave assisted syntheses, and their structures were confirmed
by NMR and HRMS. All derivatives proved to be active against both strains of the parasite. The highest
overall activity was displayed by the short chain aromatic derivative 8 (IC50 = 1.44 nM), containing only
one nitrogen atom, while long chain polyamine derivatives were found to have the lowest activity against
both strains. An interesting correlation between the IC50, pKa values and resistance index (RI) was found
URI
http://hdl.handle.net/10394/17395https://www.sciencedirect.com/science/article/pii/S0968089612004920
https://doi.org/10.1016/j.bmc.2012.06.014