Synthesis and in vitro and in vivo antimalarial activity of new 4-anilinoquinolines.
A new series of 4-anilinoquinolines with two proton-accepting side chains has been synthesized. Antimalarial activity and levels of cytotoxicity upon both MRC-5 cells and macrophages were found to be highly dependent upon the features of these side chains. Several compounds were found to be active in the low nanomolar range, against both chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro. From among them, a morpholino derivative cured mice infected by Plasmodium berghei and displayed a lower toxicity than amodiaquine upon mouse macrophages.
Delarue
S
S
Institut de Biologie et Institut Pasteur de Lille, UMR CNRS 8525, Université de Lille II, 1 rue du Professeur Calmette, B.P. 447, 59021 Lille Cedex, France.
Girault
S
S
Maes
L
L
Debreu-Fontaine
M A
MA
Labaeïd
M
M
Grellier
P
P
Sergheraert
C
C
D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D004351:Drug Resistance; D005260:Female; D006801:Humans; D017737:Macrophages, Peritoneal / Q000187:drug effects; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D051379:Mice; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000814:Aniline Compounds; D000962:Antimalarials; D011804:Quinolines