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.
Araújo
Nuna C P
NC
Centro de Ciências do Mar and Departamento de Química e Bioquímica, F.C.T, Campus de Gambelas, Universidade do Algarve, 8005-039 Faro, Portugal.
Barton
Victoria
V
Jones
Michael
M
Stocks
Paul A
PA
Ward
Stephen A
SA
Davies
Jill
J
Bray
Patrick G
PG
Shone
Alison E
AE
Cristiano
Maria L S
ML
O'Neill
Paul M
PM
D000585:Aminacrine / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D037621:Artemisinins / Q000138:chemical synthesis / Q000737:chemistry; D010545:Peroxides / Q000138:chemical synthesis / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects*; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000962:Antimalarials; D037621:Artemisinins; D010545:Peroxides; D011804:Quinolines; D000585:Aminacrine; C031327:artemisinin