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 EC 50 values from 1.1 to 4.9 mg/L, superior to that of the commercial fungicide thifluzamide (EC 50 = 23.1 mg/L). Compound 9cd (EC 50 = 0.8 mg/L) was far more active than thifluzamide (EC 50 = 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 m 2 , 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.

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Drug design | Strobilurins | Biological activity | Structure-activity relationships |Cytochrome bc 1 complexIn searching for novel fungicidal leads, a series of pyrazole-containing strobilurins were rationally designed, synthesized and characterized. Bioassay indicated that compound I-7 displayed excellent fungicidal activity against a broad spectrum of plant pathogens such as Gibberella zeae, Rhizoctonia cerealis, Sclerotinia sclerotiorum, Phytophthora infestans, Physalospora piricola and Pellicularia sasakii with EC 50 of 0.16, 0.02, 0.72, 0.07, 0.77 and 0.65 μg/mL, respectively, which were 3-10 times more potent than the positive control azoxystrobin against the corresponding pathogens. Moreover, like azoxystrobin and kresoxim methyl, I-7, displayed excellent protective activity against P. sorghi. Molecular docking validated that I-7 and azoxystrobin would share a similar binding mode with cytochrome bc 1 complex. This study demonstrates that I-7 is a promising fungicidal candidate for further development.