Discovery of novel 4-sulfur-substituted pyrazol-5-yl-benzamide derivatives containing amide/hydrazide/ester moieties as potential succinate dehydrogenase inhibitors.

BACKGROUND

Succinate dehydrogenase inhibitor (SDHI) fungicides have been widely utilized in the combat of plant pathogenic fungi due to their potent, broad-spectrum antifungal activity and unique mode of action. In this study, a series of novel 4-sulfur-substituted pyrazol-5-yl-benzamide derivatives containing amide, hydrazide, or ester moieties were synthesized to develop innovative SDH inhibitors.

RESULTS

The bioassay studies indicated that several compounds exhibited potent in vitro fungicidal activity against various fungi. Particularly, compound 4d demonstrated broad-spectrum fungicidal efficacy, with EC50 values of 0.21, 0.95, 0.64, 1.33, and 0.66 mg L-1 against Valsa mali, Botrytis cinerea, Rhizoctonia solani, Fusarium graminearum, and Gaeumannomyces graminis, respectively. In vivo studies demonstrated that compound 4d effectively prevented V. mali infection in apples at 50 mg L-1, showing superior protective and curative effects (93.4% and 85.5%) compared to lead compound A27 (68.7% and 57.0%) and commercial fungicide fluxapyroxad (55.4% and 43.6%). Enzymatic inhibition assays and molecular docking analysis suggested that compound 4d could serve as a potential SDH inhibitor.

CONCLUSION

This study offers valuable insights for expanding the fungicidal spectrum of pyrazol-5-yl-benzamide derivatives and further developing them as novel SDH inhibitors. © 2025 Society of Chemical Industry.