Synthesis and in vitro and in vivo antimalarial activity of novel 4-anilinoquinoline Mannich base derivatives

Abstract

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 4-anilinoquinoline ring. A series of novel 4-anilinoquinoline Mannich base drug molecules have been synthesized. The synthesis involves the preparation of Mannich base and these bases subsequently coupled with 4,7-dichloroquinoline to get targeted drug molecules (Burckhalter et al. in J Am Chem Soc 70:1363–1373, 1948). Their structures were confirmed by IR, NMR, and mass spectral data. 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, respectively (Charmot et al. in Prev Med 15:889, 1986). Except one molecule (containing diphenylamine), all the tested molecules showed activity while one of them (containing morpholine) showed promising in vitro and significant in vivo antimalarial activity under given test conditions.