Synthesis and in vitro and in vivo antimalarial activity of new 4-anilinoquinolines

A new series of 4-anilinoquinolines with two proton-accepting side chains h as been synthesized. Antimalarial activity and levels of cytotoxicity upon both MRC-5 cells and macrophages were found to be highly dependent upon the features of these side chains. Several compounds were found to be active i n the low nanomolar range, against both chloroquine-sensitive and -resistan t strains of Plasmodium falciparum in vitro. From among them, a morpholino derivative cured mice infected by Plasmodium berghei and displayed a lower toxicity than amodiaquine upon mouse macrophages.