title: Herbicidal properties of antimalarial drugs.
abstract: The evolutionary relationship between plants and the malarial parasite Plasmodium falciparum is well established and underscored by the P. falciparum apicoplast, an essential chloroplast-like organelle. As a result of this relationship, studies have demonstrated that herbicides active against plants are also active against P. falciparum and thus could act as antimalarial drug leads. Here we show the converse is also true; many antimalarial compounds developed for human use are highly herbicidal. We found that human antimalarial drugs (e.g. sulfadiazine, sulfadoxine, pyrimethamine, cycloguanil) were lethal to the model plant Arabidopsis thaliana at similar concentrations to market herbicides glufosinate and glyphosate. Furthermore, the physicochemical properties of these herbicidal antimalarial compounds were similar to commercially used herbicides. The implications of this finding that many antimalarial compounds are herbicidal proffers two novel applications: (i) using the genetically tractable A. thaliana to reveal mode-of-action for understudied antimalarial drugs, and (ii) co-opting antimalarial compounds as a new source for much needed herbicide lead molecules.
authors.affiliation: School of Molecular Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, Perth 6009, Australia.|The ARC Centre of Excellence in Plant Energy Biology, 35 Stirling Highway, Crawley, Perth 6009, Australia.
authors.forename: Maxime G
authors.initials: MG
authors.lastname: Corral
authors.affiliation: School of Molecular Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, Perth 6009, Australia.|The ARC Centre of Excellence in Plant Energy Biology, 35 Stirling Highway, Crawley, Perth 6009, Australia.
authors.forename: Julie
authors.initials: J
authors.lastname: Leroux
authors.affiliation: School of Molecular Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, Perth 6009, Australia.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Stubbs
authors.affiliation: School of Molecular Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, Perth 6009, Australia.|The ARC Centre of Excellence in Plant Energy Biology, 35 Stirling Highway, Crawley, Perth 6009, Australia.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Mylne
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D017360:Arabidopsis / Q000187:drug effects* / Q000469:parasitology; D006540:Herbicides / Q000494:pharmacology*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000469:parasitology; D002727:Proguanil / Q000494:pharmacology; D011739:Pyrimethamine / Q000494:pharmacology; D013411:Sulfadiazine / Q000494:pharmacology; D013413:Sulfadoxine / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D006540:Herbicides; D014227:Triazines; D013411:Sulfadiazine; C026009:cycloguanil; D013413:Sulfadoxine; D002727:Proguanil; D011739:Pyrimethamine