Antimalarial activity of floxacrine (HOE 991) II: Studies on causal prophylactic and blood schizontocidal action of floxacrine and related dihydroacridinediones against Plasmodium yoelii and P. berghei.

Abstract

The causal prophylactic and blood schizontocidal action of six dihydroacridinediones were assessed in mice using the Plasmodium yoelii 17X strain in sporozoite-induced infections and the P. berghei K 173 strain in blood-induced infections respectively. A remarkable relationship was shown between the action on pre-erythrocytic forms and on blood forms of malaria parasites. A trifluoromethyl group in the para (4—) position of the 3-phenyl ring of the 7-chloro-10-hydroxy-3,4-dihydroacridine-1,9-(2H,10H)-dione (compound Hoe 991: floxacrine) proved the most favourable substituent of a group of electronegative substituents concerning antimalarial activity. The CPD50/CD50 of Hoe 991 against pre-erythrocytic/blood forms of P.yoelii/P. berghei was 0·37 mg kg−1 (X 1)/1·7 mg kg−1 (X5) after the intraperitoneal (ip)/subcutaneous (sc) route. As demonstrated by compound Hoe 990 double substitution in the 3-phenyl ring with 2-chloro-, 4-trifluoromethyl- caused a marked residual action. The causal prophylactic effect (CP...