Antimalarial Activities of New Pyrrolo[3,2-f]Quinazoline-1,3-Diamine Derivatives

摘要: WR227825 is an antimalarial pyrroloquinazolinediamine derivative with a high potency but low therapeutic index. A series of carbamate, carboxamide, succinimide, and alkylamine derivatives were prepared to search for compounds improved The new acetamides imide showed potent cell growth inhibition against four clones Plasmodium falciparum (D-6, RCS, W-2, TM91C235), 50% inhibitory concentration approximately 0.01 ng/ml, highly active berghei, 100% cure at doses from <0.1 mg/kg body weight 220 mg/kg. carbamates alkyl derivatives, however, weak activity efficacious in tests P. berghei by the Thompson test. best compounds, bis-ethylcarbamate (compound 2a) tetra-acetamide (3a) further demonstrated sporozoite yoelii mice vivax aotus monkeys. Against AMRU-1 strain vivax, which has dihydrofolate reductase mutations resistant antifolates, 3a cured monkeys 1 3 Compound 2a only one out two results indicated that not have retained/improved efficacy parent compound also less toxic animals used tests.