Antimalarial N-1,N-3-dialkyldioxonaphthoimidazoliums: synthesis, biological activity, and structure-activity relationships
Haynes, Richard K.
Tong, Jie Xin
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Here we report the nanomolar potencies of N1,N3-dialkyldioxonaphthoimidazoliums against asexual forms of sensitive and resistant Plasmodium falciparum. Activity was dependent on the presence of the fused quinone-imidazolium entity and lipophilicity imparted by the N1/N3 alkyl residues on the scaffold. Gametocytocidal activity was also detected, with most members active at IC50 < 1 μM. A representative analog with good solubility, limited PAMPA permeability, and microsomal stability demonstrated oral efficacy on a humanized mouse model of P. falciparum
- Faculty of Health Sciences