Semi-synthetic and synthetic 1,2,4-trioxaquines and 1,2,4-trioxolaquines: synthesis, preliminary SAR and comparison with acridine endoperoxide conjugates

A novel series of semi-synthetic trioxaquines and synthetic trioxolaquines were prepared, in moderate to good yields. Antimalarial activity was evaluated against both the chloroquine-sensitive 3D7 and resistant K1 strain of Plasmodium falciparum and both series of compounds were shown to be active in the low nanomolar range. For comparison the corresponding 9-amino acridine analogues were also prepared and shown to have low nanomolar activity like their quinoline counterparts.

Graphical abstractA series of semi-synthetic trioxaquines and synthetic trioxolaquines were prepared, in moderate to good yields, and were evaluated against both the chloroquine-sensitive 3D7 and resistant K1 strain of Plasmodium falciparum. For comparison the corresponding 9-amino acridine analogues were also prepared and shown to have low nanomolar activity like their quinoline counterparts.Figure optionsDownload full-size imageDownload as PowerPoint slide