Design, Synthesis, and Evaluation of Antifungal Bioactivity of Novel Pyrazole Carboxamide Thiazole Derivatives as SDH Inhibitors

Agricultural production is seriously threatened by plantpathogens.The development of new fungicides with high efficacy and low toxicityis urgently needed. In this study, a series of pyrazole carboxamidethiazole derivatives were designed, synthesized, and evaluated fortheir antifungal activities against nine plant pathogens invitro. Bioassay results showed that most compounds (3i, 5i, 6i, 7i, 9i, 12i, 16i, 19i,and 23i) exhibited good antifungal activities against Valsa mali. In particular, compounds 6i and 19i exhibited better antifungal activities against Valsa mali with EC50 values of 1.77 and1.97 mg/L, respectively, than the control drug boscalid (EC50 = 9.19 mg/L). Additionally, compound 23i exhibited excellent inhibitory activity against Rhizoctoniasolani, with an EC50 value of 3.79 mg/L.Compound 6i at 40 mg/L showed a satisfactory in vivo protective effect against Valsa mali. Scanning electron microscopy analyses revealed that compound 6i could significantly damage the surface morphology to interferewith the growth of Valsa mali. In moleculardocking, the results showed that compound 6i interactswith TRP O: 173, SER P: 39, TYR Q: 58, and ARG P: 43 of succinatedehydrogenase (SDH) through hydrogen bonding and & sigma;-& pi;interaction, and its binding mode is similar to that of boscalid and SDH. The enzyme activity experiment also further verified itsaction mode. Our studies suggested that pyrazole carboxamide thiazolederivative 6i provided a valuable reference for the furtherdevelopment of succinate dehydrogenase inhibitors.