Dihydroartemisinin (DHA) was coupled to different aminoquinoline moieties forming hybrids 9–14,
which were then treated with oxalic acid to form oxalate salts (9a–14a). Compounds 9a, 10a, 12, 12a,
and 14a showed comparable potency in vitro to that of chloroquine (CQ) against the chloroquine sensitive (CQS) strain, and were found to be more potent against the chloroquine resistant CQR strain. Hybrids
12 and its oxalate salt 12a were the most active against CQR strain, being 9- and 7-fold more active than
CQ, respectively (17.12 nM; 20.76 nM vs 157.9 nM). An optimum chain length was identified having 2 or
3 Cs with or without an extra methylene substituent.
Dihydroartemisinin (DHA) was coupled to different aminoquinoline moieties forming hybrids 9–14,which were then treated with oxalic acid to form oxalate salts (9a–14a). Compounds 9a, 10a, 12, 12a,and 14a showed comparable potency in vitro to that of chloroquine (CQ) against the chloroquine sensitive (CQS) strain, and were found to be more potent against the chloroquine resistant CQR strain. Hybrids12 and its oxalate salt 12a were the most active against CQR strain, being 9- and 7-fold more active thanCQ, respectively (17.12 nM; 20.76 nM vs 157.9 nM). An optimum chain length was identified having 2 or3 Cs with or without an extra methylene substituent.
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