Isoxaflutole (IXF), a 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor, causes injury to crops leading to reductions in grain yield. In order to solve the phytotoxicity caused by IXF, the present work evaluated the protective response of the substituted quinoxaline derivatives as potential safeners on Zea mays. The bioassay results showed that all of the test compounds displayed protection against IXF. In particular, safener I-6 exhibited excellent safener activity against IXF injury via enhancing glutathione (GSH) content, glutathione S transferases (GSTs) and cytochrome P450 monooxygenases (CYP450) activity. The tested compounds induced the activity of CYP450 and GSTs in Z. mays. The physicochemical properties and ADMET properties of safener I-6, benoxacor and diketonitrile (DKN, IXF metabolite) were compared to predict pharmaceutical behavior. The present work demonstrates that the safener I-6 could be considered as a potential candidate for developing novel safeners in the future.

Isoxaflutole (IXF) 是一种 4-羟基苯基丙酮酸双加氧酶 (HPPD) 抑制剂，会对作物造成伤害，导致谷物产量下降。为了解决IXF引起的植物毒性，目前的工作评估了取代喹喔啉衍生物作为玉米潜在安全剂的保护反应。生物测定结果显示所有测试化合物均显示出针对 IXF 的保护作用。特别是，安全剂I-6通过提高谷胱甘肽 (GSH) 含量、谷胱甘肽 S 转移酶 (GST) 和细胞色素 P450 单加氧酶 (CYP450) 的活性，对 IXF 损伤表现出出色的安全剂活性。测试的化合物在Z. mays 中诱导了 CYP450 和 GSTs 的活性. 比较安全剂I-6、benoxacor 和二酮腈（DKN、IXF 代谢物）的理化特性和 ADMET 特性以预测药物行为。目前的工作表明，安全剂I-6可以被视为未来开发新型安全剂的潜在候选者。