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

ABSTRACT

Agricultural production is seriously threatened by plant pathogens. The development of new fungicides with high efficacy and low toxicity is urgently needed. In this study, a series of pyrazole carboxamide thiazole derivatives were designed, synthesized, and evaluated for their antifungal activities against nine plant pathogens in vitro. 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 and 1.97 mg/L, respectively, than the control drug boscalid (EC50 = 9.19 mg/L). Additionally, compound 23i exhibited excellent inhibitory activity against Rhizoctonia solani, 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 interfere with the growth of Valsa mali. In molecular docking, the results showed that compound 6i interacts with TRP O 173, SER P 39, TYR Q 58, and ARG P 43 of succinate dehydrogenase (SDH) through hydrogen bonding and σ-π interaction, and its binding mode is similar to that of boscalid and SDH. The enzyme activity experiment also further verified its action mode. Our studies suggested that pyrazole carboxamide thiazole derivative 6i provided a valuable reference for the further development of succinate dehydrogenase inhibitors.