Design, Synthesis, and Evaluation of the Antifungal Activity of Novel Pyrazole-Thiazole Carboxamides as Succinate Dehydrogenase Inhibitors.

Succinate dehydrogenase (SDH) is regarded as a promising target for fungicide discovery. To continue our ongoing studies on the discovery of novel SDH inhibitors as fungicides, novel pyrazole-thiazole carboxamides were designed, synthesized, and evaluated for their antifungal activity. The results indicated that compounds , , and showed excellent activities against with EC values from 1.1 to 4.9 mg/L, superior to that of the commercial fungicide thifluzamide (EC = 23.1 mg/L). Compound (EC = 0.8 mg/L) was far more active than thifluzamide (EC = 4.9 mg/L) against . Compound exhibited promising activity against (90% at 10 mg/L), which was better than that of thifluzamide (80% at 10 mg/L). The field experiment showed that compound had 74.4% efficacy against on the 15th day after two consecutive sprayings at an application rate of 4.80 g a.i./667 m, which was close to that of thifluzamide (83.3%). Furthermore, molecular docking explained the possible binding mode of compound in the SDH active site. Our studies indicated that the pyrazole-thiazole carboxamide hybrid is a new scaffold of SDH inhibitors.