Antimalarial Imidazopyridines Incorporating an Intramolecular Hydrogen Bonding Motif: Medicinal Chemistry and Mechanistic Studies.

ABSTRACT: We previously identified a novel class of antimalarial benzimidazoles incorporating an intramolecular hydrogen bonding motif. The frontrunner of the series, analogue A, showed nanomolar activity against the chloroquine-sensitive NF54 and multi-drug-resistant K1 strains of Plasmodium falciparum (PfNF54 IC₅₀ = 0.079 μM; PfK1 IC₅₀ = 0.335 μM). Here, we describe a cell-based medicinal chemistry structure-activity relationship study using compound A as a basis. This effort led to the identification of novel antimalarial imidazopyridines with activities of <1 μM, favorable cytotoxicity profiles, and good physicochemical properties. Analogue 14 ( PfNF54 IC₅₀ = 0.08 μM; PfK1 IC₅₀ = 0.10 μM) was iden

SUBMITTER: Attram HD 

PROVIDER: S-EPMC10111423 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature