In vitro antiplasmodial and cytotoxic activities of asymmetrical pyridinium derivatives

• Asymmetrical pyridinium compounds were found to be lethal to Plasmodium falciparum in vitro.
• Five compounds demonstrate IC50 values below 10 nM.
• SAR analyses have determined the essential parameters for their antimalarial effect.
• Compound 23 agrees to the hit-to-lead identification criteria against P. falciparum.

An in vitro investigation of the antiplasmodial and cytotoxic activities of a series of human choline kinase inhibitors against Plasmodium falciparum is reported. Structure–activity relationship analyses have allowed us to determine the essential parameters for the antimalarial effect of these asymmetrical pyridinium derivatives. One of the compounds meets the World Health Organization's criteria for hit identification against P. falciparum exhibiting an IC50 of 0.0016 μg/ml and a selectivity index of >3000.

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