Investigation into the Synthesis, Bioactivity, and Mechanism of Action of the Novel 6-Pyrazolyl-2-picolinic Acid as a Herbicide.

A series of new 4-amino-3,5-dicholo-6-(5-aryl-substituted-1H-pyrazol-1-yl)-2-picolinic acid compounds were designed and prepared to discover herbicidal molecules. The inhibitory activities of all new compounds against the root growth ofArabidopsis thaliana were assayed. On the whole, the new synthesized compounds displayed good inhibition effects and had excellent herbicidal activities on root growth of weed at 500 µM. Importantly, a selection of compounds demonstrated comparable herbicidal properties to picloram. At the dosage of 250 g/ha, most of the compounds showed a 100% postemergence herbicidal activity to control Chenopodium album and Amaranthus retroflexus. Using compound V-2, the mechanism of action was investigated based on a phenotype study using AFB5-deficient Arabidopsis thaliana. It was found that the novel 6-pyrazolyl-2-picolinic acids were auxinic compounds. In addition, it was proposed that V-2 may be an immune activator due to its upregulation of defense genes and the increased content of jasmonic acid.

Study on Design, Synthesis and Herbicidal Activity of Novel 6-Indazolyl-2-picolinic Acids.

Thirty-eight new 4-amino-3,5-dicholo-6-(1H-indazolyl)-2-picolinic acids and 4-amino-3,5-dicholo-6-(2H-indazolyl)-2-picolinic acids were designed by scaffold hopping and synthesized to discover potential herbicidal molecules. All the new compounds were tested to determine their inhibitory activities against Arabidopsis thaliana and the root growth of five weeds. In general, the synthesized compounds exhibited excellent inhibition properties and showed good inhibitory effects on weed root growth. In particular, compound 5a showed significantly greater root inhibitory activity than picloram in Brassica napus and Abutilon theophrasti Medicus at the concentration of 10 µM. The majority of compounds exhibited a 100% post-emergence herbicidal effect at 250 g/ha against Amaranthus retroflexus and Chenopodium album. We also found that 6-indazolyl-2-picolinic acids could induce the up-regulation of auxin genes ACS7 and NCED3, while auxin influx, efflux and auxin response factor were down-regulated, indicating that 6-indazolyl-2-picolinic acids promoted ethylene release and ABA production to cause plant death in a short period, which is different in mode from other picolinic acids.

Design, Synthesis, Herbicidal Activity, and Structure-Activity Relationship Study of Novel 6-(5-Aryl-Substituted-1-Pyrazolyl)-2-Picolinic Acid as Potential Herbicides.

Picolinic acid and picolinate compounds are a remarkable class of synthetic auxin herbicides. In recent years, two new picolinate compounds, halauxifen-methyl (ArylexTM active) and florpyrauxifen-benzyl (RinskorTM active), have been launched as novel herbicides. Using their structural skeleton as a template, 33 4-amino-3,5-dicholor-6-(5-aryl-substituted-1-pytazolyl)-2-picolinic acid compounds were designed and synthesized for the discovery of compounds with potent herbicidal activity. The compounds were tested for inhibitory activity against the growth of Arabidopsis thaliana roots, and the results demonstrated that the IC50 value of compound V-7 was 45 times lower than that of the halauxifen-methyl commercial herbicide. Molecular docking analyses revealed that compound V-7 docked with the receptor auxin-signaling F-box protein 5 (AFB5) more intensively than picloram. An adaptive three-dimensional quantitative structure-activity relationship model was constructed from these IC50 values to guide the next step of the synthetic strategy. Herbicidal tests of the new compounds indicated that compound V-8 exhibited better post-emergence herbicidal activity than picloram at a dosage of 300 gha-1, and it was also safe for corn, wheat, and sorghum at this dosage. These results demonstrated that 6-(5-aryl-substituted-1-pyrazolyl)-2-picolinic acid compounds could be used as potential lead structures in the discovery of novel synthetic auxin herbicides.

Design, Synthesis, Fungicidal and Insecticidal Activities of Novel Diamide Compounds Combining Pyrazolyl and Polyfluoro-Substituted Phenyl into Alanine or 2-Aminobutyric Acid Skeletons.

Thirty novel diamide compounds combining pyrazolyl and polyfluoro-substituted phenyl groups into alanine or 2-aminobutyric acid skeletons were designed and synthesized with pyflubumide as the lead compound to develop potent and environmentally friendly pesticides. The preliminary bioassay results indicated that the new compounds containing the para-hexa/heptafluoroisopropylphenyl moiety exhibit fungicidal, insecticidal, and acaricidal activities. This is the first time that the para-hexa/heptafluoroisopropylphenyl group is a key fragment of the fungicidal activity of new N-phenyl amide compounds. Most of the target compounds exhibited moderate to good insecticidal activity against Aphis craccivora at a concentration of 400 µg/mL, and some showed moderate activity at a concentration of 200 µg/mL; in particular, compounds I-4, II-a-10, and III-26 displayed higher than 78% lethal rates at 200 µg/mL. Compound II-a-14 exhibited a 61.1% inhibition at 200 µg/mL for Tetranychus cinnabarinus. In addition, some of the target compounds exhibited good insecticidal activities against Plutella xylostella at a concentration of 200 µg/mL; the mortalities of compounds I-1, and II-a-15 were 76.7% and 70.0%, respectively. Preliminary analysis of the structure-activity relationship (SAR) indicated that the insecticidal and acaricidal activities varied significantly depending on the type of substituent and substitution pattern. The fungicidal activity results showed that compounds I-1, II-a-10, II-a-17, and III-26 exhibited good antifungal effects. Enzymatic activity experiments and in vivo efficacy of compound II-a-10 were conducted and discussed.