Synthesis, Bioactivity Evaluation, 3D-QSAR, and Molecular Docking of Novel Pyrazole-4-carbohydrazides as Potential Fungicides Targeting Succinate Dehydrogenase

Main observation and conclusionTo screen novel antifungal agents targeting the succinate dehydrogenase (SDH), a series of pyrazole-4-carbohydrazides were rationally designed, synthesized, and characterized under the guidance of the structures of succinate dehydrogenase inhibitors (SDHIs). Bioassay results in vitro indicated that most of the target compounds exhibited excellent activity against Rhizoctonia solani (R. solani), Fusarium graminearum (F. graminearum), Botrytis cinerea (B. cinerea) and Colletotrichum capsica (C. cinerea). Compounds 7d, 7l, 7t and 7x were identified as the most promoting candidates, and their anti-F. graminearum EC50 values were as low as 0.56, 0.47, 0.46 and 0.49 mu g/mL, respectively, presenting the similar antifungal activity as that of the commonly used fungicide carbendazim (0.43 mu g/mL). The 3D-QSAR models were built for a systematic structure-activity relationship profile to explore more potent pyrazole-4-carbohydrazides as novel fungicides. Molecular docking of 7d, 7l and 7r with SDH was performed to reveal the binding modes in active pocket and analyze the interactions between the molecules and the SDH protein.[GRAPHICS].