2‐Amino‐ 3 H ‐phenoxazin‐3‐one is a lead inhibitor of Cuscuta campestris early development: structure–activity relationships of o ‐aminophenol‐derived allelochemicals

BACKGROUND 2‐Amino‐3 H ‐phenoxazin‐3‐one (synonym: questiomycin A; abbreviated as APO or Phx‐3) is a naturally occurring phenoxazinone‐type allelochemical with recognized potential as drug scaffold, but its value against parasitic weeds remains unexplored. Dodders, represented by species like Cuscuta campestris , are destructive parasitic plants that compromise crop productivity and quality, as well as damage to ornamental plants. Control options are limited and often rely on herbicides with sustainability and selectivity constraints. RESULTS Inspired by allelopathy as a source of eco‐compatible herbicide models, APO and a set of phenoxazinones obtained via one‐step oxidative cyclocondensation of aminophenols (6–91% yields) were evaluated on C. campestris germination and early seedling development at 100–400 μM. APO, synthesized in 70% yield from 2‐aminophenol, showed the most consistent and specific inhibitory activity on both germination and seedling growth. In addition, APO induced marked necrotic effects, which were further enhanced by its nitro‐derivative, causing around 90% necrosis across the tested concentration range. Some additional derivatives displayed moderate necrosis levels, enabling preliminary structure–activity relationship insights within the phenoxazinone scaffold, suggesting a trend in favor of lower‐cLog P structures that share similar topological polar surface area values. CONCLUSIONS This is the first evidence supporting phenoxazinones, particularly the allelochemical APO, as leads for parasitic weed and dodder management. Their synthetic accessibility at multigram scale from aminophenols, including by‐products and contaminants from industrial wastewaters like 2‐aminophenol, strengthens a real applicability from a circular‐chemistry perspective for development of active agents based on natural products in integrated control strategies for a more sustainable pest management.