1. Academic Validation
  2. Discovery of Tetrazolamide-benzimidazol-2-ones as Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors

Discovery of Tetrazolamide-benzimidazol-2-ones as Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors

  • J Agric Food Chem. 2024 Feb 28;72(8):3884-3893. doi: 10.1021/acs.jafc.3c06798.
Zhuo-Mei Cai 1 2 Guang-Yi Huang 1 2 Jin Dong 1 2 Li-Jun Chen 1 2 Bao-Qing Ye 1 2 Hong-Yan Lin 1 2 Da-Wei Wang 1 2 Guang-Fu Yang 1 2
Affiliations

Affiliations

  • 1 National Key Laboratory of Green Pesticide, Central China Normal University, Wuhan 430079, P. R. China.
  • 2 International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, P. R. China.
Abstract

4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) is one of the most valuable herbicide targets due to its unique biological functions. In search of HPPD inhibitors with promising biological performance, we designed and synthesized a series of novel tetrazolamide-benzimidazol-2-ones using a structure-based drug design strategy. Among the synthesized compounds, 1-(2-chlorobenzyl)-3-methyl-N-(1-methyl-1H-tetrazol-5-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-4-carboxamide, 25, IC50 = 10 nM, was identified to be the most outstanding HPPD Inhibitor, which showed more than 36-fold increased Arabidopsis thaliana HPPD (AtHPPD) inhibition potency than mesotrione (IC50 = 363 nM). Our AtHPPD-25 complex indicated that one nitrogen atom on the tetrazole ring and the oxygen atom on the amide group formed a classical bidentate chelation interaction with the metal ion, the benzimidazol-2-one ring created a tight π-π stacking interaction with Phe381 and Phe424, and some hydrophobic interactions were also found between the ortho-Cl-benzyl group and surrounding residues. Compound 32 showed more than 80% inhibition against all four tested weeds at 150 g ai/ha by the postemergence application. Our results indicated that the tetrazolamide-benzimidazol-2-one scaffold may be a new lead structure for herbicide discovery.

Keywords

4-hydroxyphenylpyruvate dioxygenase; benzimidazol-2-one; herbicidal activity; inhibitor; tetrazolamide.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-161308
    HPPD Inhibitor