Design and Synthesis of Novel Phthalide Derivatives containing 1,3,4-Oxadiazole/1,2,4-Triazole Units as Potential Antifungal Agents

Four series of novel 1,3,4-oxadiazole/1,2,4-triazole hybrids of phthalide derivatives were designed and synthesized to search for novel potential antifungal agents. Preliminary antifungal activity assay results showed that compounds 4 a , 4 b , 4 m , 5 b , 5 f , 5 h , and 7 h exhibited moderate to excellent inhibitory activity against some phytopathogenic fungi. Among them, compound 5 b displayed the most outstanding antifungal effects against V. mali and S. sclerotiorum , with the EC 50 mean of 3.96 μg/mL and 5.60 μg/mL, respectively, which was superior to those of commercial fungicides hymexazol and chlorothalonil. Furthermore, compound 5 b could completely suppress the spore germination of V. mali at a concentration of 10 μg/mL. Finally, molecular docking revealed that the potential target for the antifungal activity of compound 5 b was succinate dehydrogenase (SDH). This research provides novel candidate compounds for the prevention of phytopathogenic fungi. Graphical