2. Academic Validation
  3. Discovery of Cycloheptanone-Pyrrole Derivatives with α-Hydroxycarboxylate Fragments as Novel Dihydroxy Acid Dehydratase-Targeting Herbicides

Discovery of Cycloheptanone-Pyrrole Derivatives with α-Hydroxycarboxylate Fragments as Novel Dihydroxy Acid Dehydratase-Targeting Herbicides

  • J Agric Food Chem. 2025 Nov 12;73(45):28662-28669. doi: 10.1021/acs.jafc.5c05535.
He Xu 1 2,  Yanhao Hu 1 2,  Mian Wei 1 2,  Jiahao Wang 1 2,  Enpei Zhang 1 2,  Dechao Gu 1 2,  Chengyu Liu 1 2,  Jiajun Huang 1 2,  Youmei Ma 1 2,  Wei Yan 1 2,  Jiahai Zhou 3,  Yonghao Ye 1 2,  Bo He 1 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Agricultural and Forestry Biosecurity, State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, PR China.
  • 2 Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of Education, Nanjing 210095, PR China.
  • 3 School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China.
PMID: 41166564 DOI: 10.1021/acs.jafc.5c05535
Abstract

Dihydroxy acid dehydratase (DHAD) is a promising Herbicide target, but no commercial DHAD inhibitors exist yet. The natural product aspterric acid (AA) has been shown to act on DHAD, inspiring us to discover novel cycloheptanone-pyrrole compounds (6aa-6ay) featuring α-hydroxycarboxylate fragments as potential DHAD-targeting herbicides. In Arabidopsis thaliana seed germination assays, most compounds demonstrated 100% inhibition at 200 μg/mL, comparable to that of the positive control penoxsulam. In greenhouse herbicidal activity tests, compound 6ag demonstrated over 85% control effectiveness against Eclipta prostrata, Amaranthus retroflexus, and Setaria viridis at a dosage of 150 g ai/ha, while also showing safety for rice. The binding model of 6ag with DHAD is similar to that of AA with DHAD, and the Kd value of 6ag binding to DHAD is 20 μM, indicating that 6ag acts with DHAD. With both herbicidal efficacy and crop safety, 6ag represents a promising novel lead compound for DHAD inhibitors.

Keywords

cycloheptanone-pyrrole skeleton; dihydroxy acid dehydratase (DHAD); herbicidal activity; α- hydroxycarboxylate.

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