Synthesis and antimalarial activity of ethylene glycol oligomeric ethers of artemisinin
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Date
2011Author
Steyn, Minette
N’Da, David D.
Breytenbach, Jaco C.
Breytenbach, Wilma J.
Smith, Peter J.
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Show full item recordAbstract
Objectives The aim of this study was to synthesize a series of ethylene glycol ether
derivatives of the antimalarial drug artemisinin, determine their values for selected physicochemical
properties and evaluate their antimalarial activity in vitro against Plasmodium
falciparum strains.
Methods The ethers were synthesized in a one-step process by coupling ethylene glycol
moieties of various chain lengths to carbon C-10 of artemisinin. The aqueous solubility and
log D values were determined in phosphate buffered saline (pH 7.4). The derivatives were
screened for antimalarial activity alongside artemether and chloroquine against chloroquinesensitive
(D10) and moderately chloroquine-resistant (Dd2) strains of P. falciparum.
Key findings The aqueous solubility within each series increased as the ethylene glycol
chain lengthened. The IC50 values revealed that all the derivatives were active against both
D10 and Dd2 strains. All were less potent than artemether irrespective of the strain.
However, they proved to be more potent than chloroquine against the resistant strain.
Compound 8, featuring three ethylene oxide units, was the most active of all the synthesized
ethers.
Conclusions The conjugation of dihydroartemisinin to ethylene glycol units of various
chain lengths through etheral linkage led to water-soluble derivatives. The strategy did not
result in an increase of antimalarial activity compared with artemether. It is nevertheless a
promising approach to further investigate and synthesize water-soluble derivatives of artemisinin
that may be more active than artemether by increasing the ethylene glycol chain
length.
URI
http://hdl.handle.net/10394/17112https://onlinelibrary.wiley.com/doi/abs/10.1111/j.2042-7158.2010.01205.x
https://doi.org/10.1111/j.2042-7158.2010.01205.x