Design, Synthesis, and Antifungal Activity Evaluation of Novel Pyrazole Sulfonamide Derivatives Containing 1,3,4-Oxadiazole Moiety.

In this study, a series of 22 novel pyrazole sulfonamide derivatives incorporating a 1,3,4-oxadiazole moiety were designed and synthesized for the development of new antifungal agents. The target compounds were prepared by introducing the 1,3,4-oxadiazole group at the 4-position of the phenylpyrazole scaffold, followed by coupling with benzenesulfonyl chlorides. Antifungal activity evaluation revealed that compound c17 exhibited excellent efficacy against Valsa mali (EC50 = 13.49 mg/L), superior to the commercial fungicide boscalid (EC50 = 13.91 mg/L). Meanwhile, compound c11 showed significant activity against Botrytis cinerea (EC50 = 13.85 mg/L). In vivo assays demonstrated that c17 effectively controlled V. mali infection on apple fruits. Preliminary investigation into the antifungal mechanism indicated that c17 disrupts the hyphal ultrastructure, and cellular content leakage assays suggested that its action likely involves compromising the plasma membrane integrity of V. mali hyphae. These findings provide valuable insights for the development of phenylpyrazole sulfonamide fungicides bearing 1,3,4-oxadiazole pharmacophores.