De Novo Design and Synthesis of Novel Benzoxazinone Derivatives Targeting Dihydroxyacid Dehydratase.

ABSTRACT: Dihydroxyacid dehydratase (DHAD), a key enzyme in the branched-chain amino acid (BCAA) synthesis pathway, is a promising herbicide target. Currently, no commercial herbicides target DHAD, and no inhibitors are in development. Structural analysis suggests that coordination with iron-sulfur clusters and hydrophobic interactions with Tyr215 and Phe181 are crucial for inhibitor binding. Based on this model, we designed and synthesised derivatives 4aa-4bb with a benzoxazinone ring. Compound 4bb effectively inhibited Arabidopsis seed germination at 50 μg/mL, reversible by BCAA supplementation. In vitro, 4bb showed a stronger binding affinity to DHAD (K_d = 83.18 μM) than AHAS (K_d = 132.70 μM). Compound 4bb exhibits minimal side effects on wheat seed germination at lower conc

SUBMITTER: He B 

PROVIDER: S-EPMC12906841 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature