Discovery of Ternary Aromatic (Heterocyclic) Thione/Thioether Derivatives as Phloem-Mobile Fungicidal Candidates

Plant fungal diseases severely threaten global crop production. To develop novel antifungal agents, we designed and synthesized a series of novel ternary aromatic (heterocyclic) thione/thioether derivatives and evaluated their antifungal activity. Most of these compounds exhibited excellent antifungal activity in vitro against Sclerotinia sclerotiorum and Rhizoctonia cerealis. In particular, compounds C3, C7, C8, and C11 exhibited remarkable antifungal activity against S. sclerotiorum, with median effective concentration (EC50) values of 0.479, 0.476, 0.240, and 0.390 μg/mL, respectively, which were more potent than that of the positive control carbendazim (0.586 μg/mL). A further in vivo test confirmed that compound C8 possessed better protective efficacy (78.3%) than carbendazim (58.8%) at 200 μg/mL. The 3D-QSAR model highlighted the dominant role of steric effects on the antifungal activity. Further studies revealed that compound C8 is phloem-mobile, rapidly translocates to roots, and strongly inhibits sclerotial formation. In field trials, compound C8 provided significantly better control efficacy against rape sclerotinia stem rot (64.9%) than carbendazim (45.5%) at 750 g a.i./ha. This study demonstrates that compound C8 has potential as an efficient phloem-mobile fungicide.