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Development of resistance has severely limited the choice of available antimalarial drugs, which clearly highlights the urgent need of novel chemotherapeutic agents for the treatment of malaria. The purpose of this study was to develop new potential antimalarial agents with Amino-quinoline ring. A series of novel Amino-quinoline Mannich base drug molecules have been synthesized.The synthesized molecules were evaluated for in vitro and in vivo antimalarial activity against the chloroquine sensitive 3D7 (West Africa) and RKL-2 strain of Plasmodium falciparum and rodent malaria parasite Plasmodium yoelii (strain N-67) in Swiss mice model.