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.