Design, synthesis and herbicidal activity of novel cyclohexanedione derivations containing pyrazole and pyridine groups as potential HPPD inhibitors

Shuai-Tao Hou; Ling Han; Wen-Rui Li; Guang-Yu Dai; Yu Liu; Ai-Min Lu; Chun-Long Yang; Min Chen

doi:10.1007/s11030-024-10836-6

Design, synthesis and herbicidal activity of novel cyclohexanedione derivations containing pyrazole and pyridine groups as potential HPPD inhibitors

Mol Divers. 2024 Apr 13. doi: 10.1007/s11030-024-10836-6. Online ahead of print.

Authors

Shuai-Tao Hou^{1

2}, Ling Han¹, Wen-Rui Li¹, Guang-Yu Dai¹, Yu Liu^{1

2}, Ai-Min Lu^{1

2}, Chun-Long Yang^{3

4}, Min Chen^{5

6}

Affiliations

¹ College of Sciences, Nanjing Agricultural University, Nanjing, 210095, China.
² Jiangsu Key Laboratory of Pesticide Science, Nanjing Agricultural University, Nanjing, 210095, China.
³ College of Sciences, Nanjing Agricultural University, Nanjing, 210095, China. ycl@njau.edu.cn.
⁴ Jiangsu Key Laboratory of Pesticide Science, Nanjing Agricultural University, Nanjing, 210095, China. ycl@njau.edu.cn.
⁵ College of Sciences, Nanjing Agricultural University, Nanjing, 210095, China. chenmin@njau.edu.cn.
⁶ Jiangsu Key Laboratory of Pesticide Science, Nanjing Agricultural University, Nanjing, 210095, China. chenmin@njau.edu.cn.

PMID: 38609691
DOI: 10.1007/s11030-024-10836-6

Abstract

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27; HPPD) is one of the important target enzymes in the development of herbicides. To discover novel HPPD inhibitors with unique molecular, 39 cyclohexanedione derivations containing pyrazole and pyridine groups were designed and synthesized. The preliminary herbicidal activity test results showed that some compounds had obvious inhibitory effects on monocotyledon and dicotyledonous weeds. The herbicidal spectrums of the highly active compounds were further determined, and the compound G31 exhibited the best inhibitory rate over 90% against Plantago depressa Willd and Capsella bursa-pastoris at the dosages of 75.0 and 37.5 g ai/ha, which is comparable to the control herbicide mesotrione. Moreover, compound G31 showed excellent crop safety, with less than or equal to 10% injury rates to corn, sorghum, soybean and cotton at a dosage of 225 g ai/ha. Molecular docking and molecular dynamics simulation analysis revealed that the compound G31 could stably bind to Arabidopsis thaliana HPPD (AtHPPD). This study indicated that the compound G31 could be used as a lead molecular structure for the development of novel HPPD inhibitors, which provided an idea for the design of new herbicides with unique molecular scaffold.

Keywords: 4-Hydroxyphenylpyruvate dioxygenase; Herbicidal activity; Molecular docking; Pyrazole; Pyridine.

Abstract

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