Design, Synthesis, and Herbicidal Activity of N-Benzyl-5-cyclopropyl-isoxazole-4-carboxamides

Abstract

Based on the structures of isoxaflutole (IFT) and N-isobutyl-N-(4-chloro-benzyl)-4-chloro-2-pentenamide, a series of N-benzyl-5-cyclopropyl-isoxazole-4-carboxamides was designed by connecting their pharmacophores (i.e., a multitarget drug design strategy). A total of 27 N-benzyl-5-cyclopropyl-isoxazole-4-carboxamides were prepared from 5-cyclopropylisoxazole-4-carboxylic acid and substituted benzylamines, and their structures were confirmed by NMR and MS. Laboratory bioassays indicated that I-26 showed 100% inhibition against Portulaca oleracea and Abutilon theophrasti at a concentration of 10 mg/L, better than the positive control butachlor (50% inhibition for both weeds). A strong growth inhibition was observed, but a typical bleaching phenomenon of IFT could not be observed in the Petri dish assay. I-05 displayed excellent postemergence herbicidal activity against Echinochloa crusgalli and A. theophrasti at a rate of 150 g/ha, and bleaching symptoms were observed in the leaves of treated weeds. The bleaching effect of Chlamydomonas reinhardtii treated by I-05 could be reversed by adding homogentisate. Enzymatic bioassays indicated that I-05 could not inhibit 4-hydroxyphenylpyruvate dioxygenase (HPPD) activity, but II-05, an isoxazole ring-opening product of I-05, could inhibit HPPD activity with an EC50 value of 1.05 μM, similar to that of mesotrione (with an EC50 value of 1.35 μM). Detailed discussion about observed herbicidal symptoms is provided in the Results and Discussion section. This investigation provided a proof-of-concept foundation that a multitarget drug design strategy could be applied in agrochemical research.

Novel Pyrazole Amides as Potential 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors

“…Petri Dish Assay. Based on methods reported in the literature, 34,35 the herbicidal activities of target compounds A1−A26 and B1−B24 were evaluated as per the inhibition against the growth of stems and roots of P. oleracea, E. crusgalli, and A. tricolor. All seeds were sterilized with 75% alcohol and then incubated to the sprouting state in an incubator.…”

Design, Synthesis, and Herbicidal Activity of Thioether Containing 1,2,4-Triazole Schiff Bases as Transketolase Inhibitors

“…Numerous herbicides, with approximately 20 modes of actions (MOA), have been discovered and marketed from the 1950s to the 1990s . Examples of herbicidal inhibiting actions include protoporphyrinogen oxidase (PPO), , acetohydroxyacid synthase (AHAS), , acetyl-CoA carboxylase (ACCase), 4-hydroxyphenylpyruvatedioxygenase (HPPD), − and many others.…”

“…However, the long-term use of herbicides with the same MOA resulted in serious weed resistance, ,− as documented by increased global reports of weed resistance to these herbicides over the past decade. ,, Not surprisingly, the rapid emergence of herbicide resistance reduced herbicide efficacy. , Therefore, there is an urgent need for the discovery of herbicides with novel structures and MOA that have higher potency and better anti-resistance properties to control weeds. − …”

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

“…Two waterhemp populations ( Amaranthus tuberculatus ) do not respond to mesotrione in Iowa and Illinois . In contrast, HPPD inhibitors are safe for crops but they are applied only to a small minority of crops, such as corn and grain. , In addition, some weeds are not sensitive to HPPD inhibitors, such as mesotrione which has a negative effect on foxtail. , Therefore, it is urgent to develop novel HPPD inhibitors.…”

“…11,12 In addition, some weeds are not sensitive to HPPD inhibitors, such as mesotrione which has a negative effect on foxtail. 13,14 Therefore, it is urgent to develop novel HPPD inhibitors.…”