title: Semi-synthetic and synthetic 1,2,4-trioxaquines and 1,2,4-trioxolaquines: synthesis, preliminary SAR and comparison with acridine endoperoxide conjugates.
abstract: 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.
authors.affiliation: Centro de Ciências do Mar and Departamento de Química e Bioquímica, F.C.T, Campus de Gambelas, Universidade do Algarve, 8005-039 Faro, Portugal.
authors.forename: Nuna C P
authors.initials: NC
authors.lastname: Araújo
authors.forename: Victoria
authors.initials: V
authors.lastname: Barton
authors.forename: Michael
authors.initials: M
authors.lastname: Jones
authors.forename: Paul A
authors.initials: PA
authors.lastname: Stocks
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Ward
authors.forename: Jill
authors.initials: J
authors.lastname: Davies
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Bray
authors.forename: Alison E
authors.initials: AE
authors.lastname: Shone
authors.forename: Maria L S
authors.initials: ML
authors.lastname: Cristiano
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Neill
mesh_terms: 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
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D010545:Peroxides; D011804:Quinolines; D000585:Aminacrine; C031327:artemisinin