A Diverse Range of Hemozoin Inhibiting Scaffolds Act on Plasmodium falciparum as Heme Complexes.

ABSTRACT: A diverse series of hemozoin-inhibiting quinolines, benzamides, triarylimidazoles, quinazolines, benzimidazoles, benzoxazoles, and benzothiazoles have been found to lead to exchangeable heme levels in cultured Plasmodium falciparum (NF54) that ranged over an order of magnitude at the IC₅₀. Surprisingly, less active compounds often exhibited higher levels of exchangeable heme than more active ones. Quantities of intracellular inhibitor measured using the inoculum effect exhibited a linear correlation with exchangeable heme, suggesting formation of heme-inhibitor complexes in the parasite. In an effort to confirm this, the presence of a Br atom in one of the benzimidazole derivatives was exploited to image its distribution in the parasite using electron spectroscopic imagin

SUBMITTER: Openshaw R 

PROVIDER: S-EPMC7948512 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature