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The emerging resistance of crop pathogens to fungicides poses a challenge to food security and compels discovery of new antifungal compounds. Here, we show that mono-alkyl lipophilic cations (MALCs) inhibit oxidative phosphorylation by affecting NADH oxidation in the plant pathogens  Zymoseptoria tritici ,  Ustilago maydis  and  Magnaporthe oryzae . One of these MALCs, consisting of a dimethylsulfonium moiety and a long alkyl chain (C 18 -SMe 2  + ), also induces production of reactive oxygen species at the level of respiratory complex I, thus triggering fungal apoptosis. In addition, C 18 -SMe 2  +  activates innate plant defense. This multiple activity effectively protects cereals against Septoria tritici blotch and rice blast disease. C 18 -SMe 2  +  has low toxicity in  Daphnia magna , and is not mutagenic or phytotoxic. Thus, MALCs hold potential as effective and non-toxic crop fungicides.

A lipophilic cation protects crops against fungal pathogens by multiple modes of action