Synthesis and antimalarial activity of carbamate and amide derivatives of 4-anilinoquinoline.
A series of 4-anilinoquinolines bearing an amino side chain linked to the aromatic ring with a carbamate or an amide bond were synthesized and evaluated for their antimalarial activity and their cytotoxicity upon MRC-5 cells. Among the 17 compounds, a majority was found to be active in the low nanomolar range against both chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro with relative low cytotoxicity. Two compounds were then tested on mice infected by Plasmodium berghei and were found to exhibit reasonable in vivo activity.
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.
Grellier
Philippe
P
Maes
Louis
L
Mouray
Elisabeth
E
Sergheraert
Christian
C
Melnyk
Patricia
P
D000577:Amides / Q000737:chemistry*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002219:Carbamates / Q000737:chemistry*; D002460:Cell Line; D005260:Female; D006801:Humans; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects*; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship
D000577:Amides; D000962:Antimalarials; D002219:Carbamates; D011804:Quinolines