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.
Sci Rep. 2017 Mar 31;7:45871. doi: 10.1038/srep45871.
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.
植物与疟原虫之间的进化关系是明确的，这一点被疟原虫的质体（apicoplast）所强调，质体是一种必要的类叶绿体细胞器。由于这种关系，研究表明，对植物有效的除草剂也对疟原虫有效，因此可以作为抗疟药物的先导。在这里，我们还证明了相反的情况也是如此；许多为人类开发的抗疟药物对植物具有高度的除草活性。我们发现，人类抗疟药物（如磺胺嘧啶、磺胺多辛、乙胺嘧啶、环氯胍）在与市场上的除草剂草甘膦和草铵膦相似的浓度下对模式植物拟南芥是致命的。此外，这些具有除草活性的抗疟化合物的物理化学性质与商业上使用的除草剂相似。这一发现表明，许多抗疟化合物具有除草活性，这有两个新的应用：（i）利用遗传上易于操作的拟南芥来揭示研究较少的抗疟药物的作用模式，以及（ii）将抗疟化合物作为一种新的来源，以获得急需的除草剂先导分子。
