2. Academic Validation
  3. Design, Synthesis, and Biological Activity of Novel Thiazole Sulfonamide Derivatives as Potent Fungicide Candidates against Sclerotinia sclerotiorum

Design, Synthesis, and Biological Activity of Novel Thiazole Sulfonamide Derivatives as Potent Fungicide Candidates against Sclerotinia sclerotiorum

  • J Agric Food Chem. 2025 Nov 19;73(46):29935-29945. doi: 10.1021/acs.jafc.5c08311.
Yanhong Ni 1,  Hongzhao Zhang 1,  Xinqi Hao 1,  Yongmin Xu 1,  Ruihan Xie 1,  Bo Ren 1,  Xingyu Chen 1,  He Liu 1,  Wei Liu 1 2 3,  Xinghai Li 1 2 3
Affiliations

Affiliations

  • 1 Department of Pesticide Science, College of Plant Protection, Shenyang Agricultural University, Shenyang, Liaoning 110866, China.
  • 2 Biopesticide Engineering Technology Research Center of Liaoning Province, Shenyang, Liaoning 110866, China.
  • 3 Shenyang Key Laboratory of Surveillance and Management for Vegetable Diseases and Insect Pests, Shenyang, Liaoning 110866, China.
PMID: 41187972 DOI: 10.1021/acs.jafc.5c08311
Abstract

Sclerotinia sclerotiorum is one of the most devastating plant pathogens, causing a severe reduction in the quality and yield of oilseed rape. To develop novel fungicide candidates against S. sclerotiorum, 58 novel thiazole sulfonamide derivatives were designed and synthesized via an active substructure splicing strategy. In vitro Antifungal bioassays demonstrated that these compounds exhibited significant inhibitory activity against S. sclerotiorum. Notably, compound 3d-1 showed the highest Antifungal potency with an EC50 value of 1.86 mg/L, which was comparable to that of the commercial fungicide thifluzamide (1.84 mg/L). In vivo bioassays further revealed that compounds 3d-1 and 3d-9 exerted excellent protective efficacy (95.7, 89.8%) and curative efficacy (80.9, 78.9%) against S. sclerotiorum on oilseed rape seedlings, which were superior to the positive control thifluzamide (89.6, 62.4%) but still inferior to fluxapyroxad (100, 90.0%). Morphological observations revealed that compound 3d-1 induced severe ultrastructural damage to the mycelia and mitochondria of S. sclerotiorum. Determination of Reactive Oxygen Species (ROS) levels and measurements of mitochondrial membrane potential (MMP), as well as fluorescence quenching experiments, were combined to elucidate the inhibitory effect of compound 3d-1 on Succinate Dehydrogenase (SDH). Enzymatic inhibition assays targeting SDH further confirmed that compound 3d-1 suppressed the activity of SsSDH, with an IC50 value of 4.14 mg/L. Moreover, molecular docking analysis demonstrated significant interactions between compound 3d-1 and the target protein SsSDH, which provides critical insights into the potential mode of action of this compound. This study provides a promising foundation for the development of Succinate Dehydrogenase Inhibitor (SDHI)-based fungicides against S. sclerotiorum.

Keywords

Sclerotinia sclerotiorum; bioassay; fungicide; succinate dehydrogenase inhibitor; thiazole sulfonamide.

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