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

Abstract

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 <b>9ac</b>, <b>9bf</b>, and <b>9cb</b> showed excellent <i>in vitro</i> activities against <i>Rhizoctonia cerealis</i> 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 <b>9cd</b> (EC₅₀ = 0.8 mg/L) was far more active than thifluzamide (EC₅₀ = 4.9 mg/L) against <i>Sclerotinia sclerotiorum</i>. Compound <b>9ac</b> exhibited promising <i>in vivo</i> activity against <i>Rhizoctonia solani</i> (90% at 10 mg/L), which was better than that of thifluzamide (80% at 10 mg/L). The field experiment showed that compound <b>9ac</b> had 74.4% efficacy against <i>Rhizoctonia solani</i> 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 <b>9ac</b> in the <i>Rc</i>SDH active site. Our studies indicated that the pyrazole-thiazole carboxamide hybrid is a new scaffold of SDH inhibitors.