Herbicidal properties of antimalarial drugs

Maxime G. Corral, Julie Leroux, Keith A. Stubbs, Joshua S. Mylne

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Article number45871
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 31 Mar 2017

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Antimalarials
Herbicides
Plasmodium falciparum
glyphosate
Arabidopsis
Apicoplasts
Sulfadiazine
Chloroplasts
Organelles
Parasites

Cite this

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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.",
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Herbicidal properties of antimalarial drugs. / Corral, Maxime G.; Leroux, Julie; Stubbs, Keith A.; Mylne, Joshua S.

In: Scientific Reports, Vol. 7, 45871, 31.03.2017.

Research output: Contribution to journalArticle

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