We have previously described several potent dual inhibitors of Plasmodium falciparum (Pf) growth characterized by the presence of statin, a β-hydroxyl amino acid able to inhibit parasite's plasmepsins (PLM). While investigating the mechanism of action of these inhibitors new compounds deprived of statin were synthetized which lost the ability to inhibit PLM, but retained a significant Pf growth inhibition. Further structural simplifications showed that the inhibition of Pf viability was to ascribe to a new pharmacophore never described before as antimalarial