Study on Design, Synthesis, and Herbicidal Activity of 4-Amino-3,5-dichloro-6-indolyl-2-picolinic Acids

Through strategically introducing an indole fragment into picloram for developing a novel auxin herbicidal molecule, a series of 4-amino-3,5-dichloro-6-indolyl-2-picolinic acids were designed and synthesized. Bioassay showed that compound VI-2 exhibited 10-fold higher root growth inhibitory activity than picloram against four weeds and over twice against Arabidopsis thaliana (A. thaliana). In postemergence trials, VI-2 and VI-6 maintained comparable herbicidal activity to picloram at a dosage of 250 g/ha. Molecular docking suggested that VI-2 formed hydrogen-bonding interactions with both TIR1 and AFB5, and its binding affinity for AFB5 was slightly higher than that of picloram (-7.63 kcal/mol vs -7.00 kcal/mol). Transcriptome analysis revealed that VI-2 activated auxin signaling and induced stress-responsive transcriptional changes, acting as both an auxinic herbicidal molecule and a potential immune activator. These findings provide a theoretical basis and new insights for optimizing 2-picolinic acid derivatives to develop new auxinic herbicidal molecules.