Antimalarial activity of 10-alkyl/aryl esters and -aminoethylethers of artemisinin

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 10α-n-propyl 11 and 10α-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.

Graphical abstractA series of 10α-n-alkyl/aryl esters and 10β-aminoethylethers of artemisinin were synthesized and their in vitro antimalarial activity as well as cytotoxicity were determined.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Synthesis of series of C-10 esters and aminoethylethers of artemisinin. ► In vitro antimalarial activity evaluation against CQS 3D7 and CQR K1 strains. ► All derivatives more potent than artemether against both strains. ► n-Propyl ester most active of all derivatives. ► n-Propyl ester 22-fold more potent than artesunate against K1.