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ID: ALA4334542

Journal: ACS Med Chem Lett

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

Authors: Ahenkorah S, Coertzen D, Tong JX, Fridianto K, Wittlin S, Birkholtz LM, Tan KSW, Lam Y, Go ML, Haynes RK.

Abstract: Here we report the nanomolar potencies of N 1,N 3-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.

CiteXplore: 31938463

DOI: 10.1021/acsmedchemlett.9b00457