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 9ac, 9bf, and 9cb showed excellent in vitro activities against Rhizoctonia cerealis with EC50 values from 1.1 to 4.9 mg/L, superior to that
of the commercial fungicide thifluzamide (EC50 = 23.1 mg/L).
Compound 9cd (EC50 = 0.8 mg/L) was far more
active than thifluzamide (EC50 = 4.9 mg/L) against Sclerotinia sclerotiorum. Compound 9ac exhibited promising in vivo activity against Rhizoctonia solani (90% at 10 mg/L), which was better
than that of thifluzamide (80% at 10 mg/L). The field experiment showed
that compound 9ac had 74.4% efficacy against Rhizoctonia solani on the 15th day after two consecutive
sprayings at an application rate of 4.80 g a.i./667 m2,
which was close to that of thifluzamide (83.3%). Furthermore, molecular
docking explained the possible binding mode of compound 9ac in the RcSDH active site. Our studies indicated
that the pyrazole–thiazole carboxamide hybrid is a new scaffold
of SDH inhibitors.