Fragmenlt Recombination Design, Synthesis, and Safener Activity of Novel Ester-Substituted Pyrazole Derivatives

Abstract

Fenoxaprop-p-ethyl (FE), a type of acetyl-CoA carboxylase (ACCase) inhibitor, has been extensively applied to a variety of crop plants. It can cause damage to wheat (Triticum aestivum) even resulting in the death of the crop. On the prerequisite of not reducing herbicidal efficiency on target weed species, herbicide safeners selectively protect crops from herbicide injury. Based on fragment splicing, a series of novel substituted pyrazole derivatives was designed to ultimately address the phytotoxicity to wheat caused by FE. The title compounds were synthesized in a one-pot way and characterized via infrared spectroscopy, 1 H nuclear magnetic resonance, 13 C nuclear magnetic resonance, and high-resolution mass spectrometry. The bioactivity assay proved that the FE phytotoxicity to wheat could be reduced by most of the title compounds. The molecular docking model indicated that compound IV-21 prevented fenoxaprop acid (FA) from reaching or acting with ACCase. The absorption, distribution, metabolism, excretion, and toxicity predictions demonstrated that compound IV-21 exhibited superior pharmacokinetic properties to the commercialized safener mefenpyr-diethyl. The current work revealed that a series of newly substituted pyrazole derivatives presented strong herbicide safener activity in wheat. This may serve as a potential candidate structure to contribute to the further protection of wheat from herbicide injury.

The safener isoxadifen‐ethyl confers fenoxaprop‐p‐ethyl resistance on a biotype of Echinochloa crus‐galli

“…19 The compound IV-2, a substituted pyrazole derivative, showed the greatest activity against fenoxapropp-ethyl and enhanced the tolerance of wheat, enhancing the GST and CytP450 activities. 20 The detoxification mechanism is also present in some weeds, mainly in grasses, that have evolved herbicide resistance. 8 Poaceae species can be considered as more prone to evolve metabolic herbicide resistance due to the greater number of CYP genes in comparison with dicots.…”

“…In corn N ‐tosyloxazolidine‐3‐carboxamide derivatives showed significant protection against tribenuron‐methyl, enhancing the glutathione content and GST activity 19 . The compound IV‐2, a substituted pyrazole derivative, showed the greatest activity against fenoxaprop‐ p ‐ethyl and enhanced the tolerance of wheat, enhancing the GST and CytP450 activities 20 . The detoxification mechanism is also present in some weeds, mainly in grasses, that have evolved herbicide resistance 8 .…”

Design, Synthesis, Structure–Activity Relationship, Molecular Docking, and Herbicidal Evaluation of 2-Cinnamoyl-3-Hydroxycyclohex-2-en-1-one Derivatives as Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors

“…For HPPD inhibitors, the molecular structure of the designed lead compound is similar to the activity structure of commercial HPPD inhibitors, and both of them produce similar coordination effects when combined with HPPD to closely bind to the active cavity of the enzyme and then exhibit inhibitory activity . This technology has been widely and successfully used in the design of drugs. − Two series of aryloxyacetic acid derivatives have been obtained by combining the aromatic oxygen fragments of herbicide 2,4-D with the pyrazole part of bipyrazone or the triketone part of mesotrione in 2020, and some of the resulting compounds have verified better herbicidal activity than mesotrione …”

Synthesis and biological activity of novel hydantoin cyclohexyl sulfonamide derivatives as potential antimicrobial agents in agriculture

“…14,15 It is speculated that the hydantoin moiety has an important role in the inhibitory activity. Thus, the hydantoin fragment has always been introduced into lead compounds in the design of agricultural pharmaceuticals to improve their antimicrobial activity [16][17][18] (Figure 1).…”