4-O-α-Thevetopyranosyldiphyllin from Taiwania flousiana: A Novel β-Tubulin Inhibitor with Broad-Spectrum Herbicidal Activity for Sustainable Weed Management.

Synthetic herbicides pose environmental and health risks, driving the search for safer plant-derived alternatives. We isolated a novel aryltetralin lactone lignan from Taiwania flousiana, identified as 4-O-α-thevetopyranosyldiphyllin. The compound showed potent pre- and postemergence herbicidal activity against 13 monocot and dicot weeds, with IC50 values ranging from 0.18 to 4.72 μg/mL. Under greenhouse conditions, foliar application at 80 μg/mL for 7 days achieved over 85% inhibition in two test weeds, comparable to glyphosate. It exhibited systemic translocation and selectivity in crops such as rice. Soil degradation half-lives were 25.1 days in paddy soil and 63.0 days in vegetable soil. The compound disrupted microtubule organization by inhibiting tubulin polymerization, specifically binding to β-tubulin (TUB7) with a high affinity of -8.30 kcal/mol, as confirmed by molecular docking and dynamics simulations. These results indicated that 4-O-α-thevetopyranosyldiphyllin was a promising lead compound for the development of a new class of systemic herbicides targeting β-tubulin.