Design, Synthesis, and Fungicidal Activity of Pyrimidinamine Derivatives as Novel Complex I Inhibitors

  • J Agric Food Chem. 2026 Jun 24;74(24):18551-18563. doi: 10.1021/acs.jafc.5c14425.
Wen-Feng Jia  1 ,  Yu-Shun Xia  1 ,  Qiang-Hui Lu  2 ,  Wei Wang  1 ,  En-Ming Lv  1 ,  Jing-Wen Zhang  1 ,  Shengnan Jin  1 ,  Yuan-Qing Xu  1 ,  Peng-Fei Zhang  1 ,  Changling Liu  3 ,  Zhong Jin  4 ,  Zhong-Yan Cao  1
Affiliations
  • 1. College of Chemistry and Molecular Sciences, Henan University, Kaifeng 475004, China.
  • 2. State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
  • 3. Shenyang Research Institute of Chemical Industry, Shenyang 110022, China.
  • 4. College of Chemistry, Xinjiang University, Urumqi 830046, China.
PMID: 42267947 DOI: 10.1021/acs.jafc.5c14425
Abstract

To develop novel fungicides targeting complex I, a series of pyrimidinamine derivatives bearing a dichloropropene ether moiety were designed and synthesized via the intermediate derivatization method. Their structures were confirmed by 1H/13C NMR, elemental analysis, HRMS, and single-crystal X-ray diffraction. Bioassays showed that several compounds exhibited excellent activity against wheat powdery mildew. Notably, compound 3 (EC50 = 0.440 mg/L) was significantly more potent than propiconazole (EC50 = 5.99 mg/L) and diflumetorim (EC50 = 4.12 mg/L). Structure-activity relationships were analyzed and further supported by molecular docking. DFT calculations indicated higher reactivity and stronger protein-binding ability for compound 3, consistent with its bioactivity. Transcriptome analysis of Blumeria graminis revealed differentially expressed genes (DEGs) enriched in pathways related to complex I, suggesting it as the potential target. Overall, compound 3 could be a promising agrochemical fungicide candidate for further development.

Keywords
complex I; dichloropropene ether; fungicidal activity; intermediate derivatization method; pyrimidinamine derivatives.
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