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 i...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2009-04, Vol.19 (7), p.2038-2043
Main Authors: ARAUJO, 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
Format: Article
Language:English
Subjects:
Aminacrine - chemical synthesis
Aminacrine - chemistry
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimalarials - chemical synthesis
Antimalarials - chemistry
Antimalarials - pharmacology
Antiparasitic agents
Artemisinins - chemical synthesis
Artemisinins - chemistry
Biological and medical sciences
Medical sciences
Peroxides - chemical synthesis
Peroxides - chemistry
Pharmacology. Drug treatments
Plasmodium falciparum
Plasmodium falciparum - drug effects
Quinolines - chemical synthesis
Quinolines - chemistry
Quinolines - pharmacology
Structure-Activity Relationship
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Summary: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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2009.02.013