Antimalarial N 1 , N 3 -Dialkyldioxonaphthoimidazoliums: Synthesis, Biological Activity, and Structure-activity Relationships

Here we report the nanomolar potencies of , -dialkyldioxonaphthoimidazoliums against asexual forms of sensitive and resistant . Activity was dependent on the presence of the fused quinone-imidazolium entity and lipophilicity imparted by the N /N alkyl residues on the scaffold. Gametocytocidal activity was also detected, with most members active at IC < 1 μM. A representative analog with good solubility, limited PAMPA permeability, and microsomal stability demonstrated oral efficacy on a humanized mouse model of .