Discovery, validation, and mechanistic investigation of 5‐fluorobenzothiazol‐2‐amine as a potential lead compound for pre‐emergence herbicide development

BACKGROUND: The discovery of lead compounds is critical for the development of new herbicides. To obtain novel potential lead compounds, herbicidal activities of a series of benzothiazole derivatives were evaluated in this study. Mechanistic investigation and structural optimization were subsequently conducted for the most active compound. RESULTS: ) of Bidens pilosa L. seedlings among all tested compounds. It also showed good crop selectivity, with no significant inhibitory effect on the growth of maize seedlings. Compound C25 treatment caused severe damage in the root tip of B. pilosa, including cell viability decrease and cell membrane integrity loss due to the excessive reactive oxygen species accumulation. Transcriptomic analysis results revealed that the expression level of key genes in auxin signal transduction pathway, including members of the AUX/IAA, ARF, GH3, and SAUR families, were significantly altered in seedlings of C25-treated group. Molecular docking further identified that auxin influx carrier 1 (AUX1) is a possible target protein. Finally, a series of C25 derivatives were designed and synthesized, and part of the derivatives also exhibited marked herbicidal activity. CONCLUSION: Compound C25 is a new potential lead compound for the development of novel pre-emergence herbicides with potent activity, good selectivity, synthetic accessibility and structural modifiability. It may inhibit weed seedling growth through a unique dual mechanism including the induction of excessive oxidative stress and the disruption of IAA signal transduction pathway. © 2026 Society of Chemical Industry.