Novel Diphenyl Ether Carbonyl Ester Fragment as a Promising Skeleton Targeting Succinate Dehydrogenase

Succinate dehydrogenase (SDH) is a globally recognized critical target for fungicides. Our research mainly focuses on discovering novel molecular skeletons targeting SDH. We designed a series of diphenyl ether ester derivatives that exhibit potential efficacy against Rhizoctonia solani by utilizing a bioisosteric approach. These results indicate that compounds with shorter linkers significantly enhance the antifungal activity. Furthermore, the antifungal potential of an ester-linked compound was superior to its amide and N-(alkoxy) counterparts. Specifically, compound ba achieved a remarkable 92% efficacy in controlling R. solani at a dosage of 50 μg/mL with an EC₅₀ value of 0.44 μg/mL, thus outperforming boscalid without negatively impacting rice growth. Moreover, ba caused significant damage to the R. solani mycelium and demonstrated an IC₅₀ value of 1.69 μM against R. solani SDH, exhibiting efficacy comparable to that of boscalid. These results unveil a promising avenue for replacing traditional heterocyclic amide-based inhibitors, potentially heralding a new generation of SDH-targeting fungicides.