Novel primaquine derivatives (PRIMACINS) obtained by conjugation of primaquine's aliphatic amine with different cinnamic acids resulted in increased in vitro activity compared to primaquine against liver-stage malarial parasites. The compounds were two- or more-fold more potent than primaquine against liver-stage P. berghei and non-cytotoxic to Huh7 human hepatoma cells. Regarding erythrocytic-stage activity against P. falciparum, only compound 5c displayed an IC50 below 10 mM, which was one order of magnitude higher than that of artemisinin. These results suggest PRIMACINS are a promising new class of agents for the treatment and prevention of malaria.