8h6a

Publication Abstract from PubMed

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, IC(50) = 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 (IC(50) = 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 pi-pi 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.

Discovery of Tetrazolamide-benzimidazol-2-ones as Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors.,Cai ZM, Huang GY, Dong J, Chen LJ, Ye BQ, Lin HY, Wang DW, Yang GF J Agric Food Chem. 2024 Feb 28;72(8):3884-3893. doi: 10.1021/acs.jafc.3c06798. , Epub 2024 Feb 20. PMID:38375801^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.