1. Antimalarial activity of 10-alkyl/aryl esters and – aminoethylethers of artemisinin
- Author
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R. Kiplin Guy, Martina Sigal, Henk J. Krebs, Theunis T. Cloete, Michele Connelly, David D. N'Da, Amy Orcutt, Julie Clark, 13061372 - Cloete, Theunis Theodorus, and 20883072 - N'Da, David Dago
- Subjects
Cell Survival ,Stereochemistry ,medicine.medical_treatment ,Cytotoxicity ,Plasmodium falciparum ,Dihydroartemisinin ,Artesunate ,Ozonide ,Ether ,Biochemistry ,Cell Line ,Antimalarials ,chemistry.chemical_compound ,Drug Discovery ,parasitic diseases ,medicine ,Humans ,Potency ,Artemether ,Malaria, Falciparum ,Artemisinin ,Molecular Biology ,biology ,Aryl ,Organic Chemistry ,biology.organism_classification ,Artemisinins ,chemistry ,medicine.drug - Abstract
A series of n-alkyl/aryl esters were synthesized and their in vitro antiplasmodial activity was measured alongside that of previously synthesized aminoethylethers of artemisinin ozonides against various strains of Plasmodium falciparum. The cytotoxicity against human cell lines was also assessed. The esters were synthesized in a one-step reaction by derivatization on carbon C-10 of dihydroartemisinin. Both classes were active against both the 3D7 and K1 strains of P. falciparum, with all compounds being significantly more potent than artemether against both strains. The majority of compounds possessed potency either comparable or more than artesunate with a high degree of selectivity towards the parasitic cells. The 10a-n-propyl 11 and 10a-benzyl 18 esters were the most potent of all synthesized ozonides, possessing a moderate ( 3-fold) and significant (22- and 12-fold, respectively) potency increases against the 3D7 and K1 strains, respectively, in comparison with artesunate. http://www.journals.elsevier.com/bioorganic-chemistry/
- Published
- 2013