Synthesis and antimalarial activity of new analogues of amodiaquine.
In order to determine the real significance of the 4'-phenolic group in the antimalarial activity and/or cytotoxicity of amodiaquine (AQ), analogues for which this functionality was shifted or modified were synthesized. Good in vitro antimalarial activity was obtained for compounds unable to form intramolecular hydrogen bond. Among the compounds synthesized, new amino derivative 5 displayed the greatest selectivity index towards the most CQ-resistant strain tested and was active in mice infected by Plasmodium berghei.
Delarue-Cochin
Sandrine
S
UMR CNRS 8525, Université de Lille II, Institut Pasteur de Lille 1 rue du Professeur Calmette, B.P. 447, 59021 Lille cedex, France.
Paunescu
Emilia
E
Maes
Louis
L
Mouray
Elisabeth
E
Sergheraert
Christian
C
Grellier
Philippe
P
Melnyk
Patricia
P
D000655:Amodiaquine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects
D000962:Antimalarials; D000655:Amodiaquine