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.