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.

Keywords

Antimalarial Resistance Plasmodium falciparum Drug-hybrid

URI

http://hdl.handle.net/10400.1/4242

Citation

Araújo, Nuna C.P.; Barton, Victoria; Jones, Michael; Stocks, Paul A.; Ward, Stephen A.; Davies, Jill; Bray, Patrick G.; Shone, Alison E.; Cristiano, Maria L.S.; O’Neill, Paul M. Semi-synthetic and synthetic 1,2,4-trioxaquines and 1,2,4-trioxolaquines: synthesis, preliminary SAR and comparison with acridine endoperoxide conjugates, Bioorganic & Medicinal Chemistry Letters, 19, 7, 2038-2043, 2009.