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

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 ?M. A representative analog with good solubility, limited PAMPA permeability, and microsomal stability demonstrated oral efficacy on a humanized mouse model of P. falciparum.

SUBMITTER: Ahenkorah S

PROVIDER: S-EPMC6956359 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Ahenkorah Stephen S Coertzen Dina D Tong Jie Xin JX Fridianto Kevin K Wittlin Sergio S Birkholtz Lyn-Marie LM Tan Kevin S W KSW Lam Yulin Y Go Mei-Lin ML Haynes Richard K RK

ACS medicinal chemistry letters 20191211 1

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 ...[more]

PMID: 31938463

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