A herbicide structure-activity analysis of the antimalarial lead compound MMV007978 against Arabidopsis thaliana

作者：Corral, Maxime G.; Leroux, Julie; Tresch, Stefan; Newton, Trevor; Stubbs, Keith A.^*; Mylne, Joshua S.^*

来源：Pest Management Science, 2018, 74(7): 1558-1563.

DOI：10.1002/ps.4872

• herbicide resistance
• antimalarial
• Arabidopsis thaliana
• Plasmodium
• Medicines for Malaria Venture

BACKGROUNDTo fight herbicide-resistant weeds, new herbicides are needed; particularly ones with new modes of action. Building on the revelation that many antimalarial drugs are herbicidal, here we focus on the Medicines for Malaria Venture antimalarial lead compound MMV007978 that has herbicidal activity against the model plant Arabidopsis thaliana.
RESULTSTwenty-two variations of the lead compound thiophenyl motif revealed that change was tolerated provided ring size and charge were retained. MMV007978 was active against select monocot and dicot weeds, and physiological profiling indicated that its mode of action is related to germination and cell division. Of interest is the fact that the compound has a profile that is currently not found among known herbicides.
CONCLUSIONWe demonstrate that the antimalarial compound MMV007978 is also herbicidal and that exploiting lead compounds that are often understudied could lead to the identification of interesting herbicidal scaffolds. Further structural investigation of MMV007978 could provide improved herbicidal chemistries with a potential new mode of action.

• 出版日期2018-7