Antimalarial in-vivo activity of bis(9-amino-6-chloro-2-methoxyacridines).
In the fight against malaria, chemotherapy using bisacridines may represent an alternative method to overcoming chloroquine-resistance. Eight bis(9-amino-6-chloro-2-methoxyacridines), in which acridine moieties were linked by polyamines substituted with a side chain, were tested for their in-vivo activity upon mice infected by Plasmodium berghei. Three of the compounds revealed antimalarial activity but no relationship could be deduced from a comparison of in-vitro and in-vivo activities. N-alkylation of the central amino group generated toxicity and, therefore, only compounds N-acylated in this position can be selected as leads.
Girault
S
S
UMR 8525 CNRS-Université de Lille II-Institut de Biologie et Institut Pasteur de Lille, France.
Delarue
S
S
Grellier
P
P
Berecibar
A
A
Maes
L
L
Quirijnen
L
L
Lemiere
P
P
Debreu-Fontaine
M A
MA
Sergheraert
C
C
D000609:Aminoacridines / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects*
D000609:Aminoacridines; D000962:Antimalarials; C010847:9-amino-6-chloro-2-methoxyacridine; D002738:Chloroquine