title: The anti-malarial activity of bivalent imidazolium salts.
abstract: A series of compounds containing bivalent imidazolium rings and one triazolium analog were synthesized and evaluated for their ability to inhibit the replication of Plasmodium falciparum cultures. The activity and selectivity of the compounds for P. falciparum cultures were found to depend on the presence of electron-deficient rings that were spaced an appropriate distance apart. The activity of the compounds was not critically dependent on the nature of the linker between the electron-deficient rings, an observation that suggests that the rings were responsible for the primary interaction with the molecular target of the compounds in the parasite. The bivalent imidazolium and triazolium compounds disrupted the process whereby merozoites gain entry into erythrocytes, however, they did not appear to prevent merozoites from forming. The compounds were also found to be active in a murine Plasmodium berghei infection, a result consistent with the compounds specifically interacting with a parasite component that is required for replication and is conserved between two Plasmodium species.
authors.affiliation: Department of Chemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6.
authors.forename: Jason Z
authors.initials: JZ
authors.lastname: Vlahakis
authors.forename: Simona
authors.initials: S
authors.lastname: Mitu
authors.forename: Gheorghe
authors.initials: G
authors.lastname: Roman
authors.forename: E
authors.initials: E
authors.lastname: Patricia Rodriguez
authors.forename: Ian E
authors.initials: IE
authors.lastname: Crandall
authors.forename: Walter A
authors.initials: WA
authors.lastname: Szarek
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000469:parasitology; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D016778:Malaria, Falciparum / Q000188:drug therapy*; D013058:Mass Spectrometry; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D007093:Imidazoles; D014230:Triazoles