Isoxaflutole II 的作用方式。异恶唑草酮的二酮腈衍生物对胡萝卜 4-羟基苯基丙酮酸双加氧酶的抑制作用表征,Pesticide Biochemistry and Physiology

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Isoxaflutole II 的作用方式。异恶唑草酮的二酮腈衍生物对胡萝卜 4-羟基苯基丙酮酸双加氧酶的抑制作用表征
Pesticide Biochemistry and Physiology ( IF 4.2 ) Pub Date : 1998-11-01 , DOI: 10.1006/pest.1998.2375
F. Viviani , J.P. Little , K.E. Pallett

摘要 Isoxaflutole（5-环丙基异恶唑-4-基2-甲磺酰基-4-三氟甲基苯基酮）是一种新型除草剂，通过抑制4-羟基苯基丙酮酸双加氧酶（HPPD）来防治玉米和甘蔗的阔叶杂草和禾本科杂草。在植物和土壤中，异恶唑草酮会迅速转化为二酮腈衍生物 (DKN)，这是活性除草剂的主要成分。DKN 体外抑制胡萝卜 HPPD 的动力学表明，它是一种有效的紧密结合抑制剂（IC50 值为 4.9 ± 0.2 nM），与处于亚铁状态的酶具有时间依赖性相互作用。其他研究提供的证据表明 DKN 是一种竞争性抑制剂，可迅速使酶失活（以 0.2 ± 0 的恒定结合率。004 μM-1s-1) 通过形成可逆复合物，缓慢释放未修饰形式的抑制剂。脱羧与分子氧的还原通常被认为是 HPPD 催化反应的第一个酶促事件，当 4-羟基苯基丙酮酸通过酮酸功能与蛋白质的内部铁结合时发生。isoxaflutole 的 DKN 具有 β-(1,3)-二酮部分，这是一种离域 π 系统，可以模拟底物的酮酸功能，并且以其铁螯合特性而闻名。由于该抑制剂与底物竞争结合，因此它很可能通过形成稳定的离子-偶极电荷转移复合物（类似于初始底物-铁复合物或早期反应中间体）与活性位点中的亚铁铁强烈螯合。

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The Mode of Action of Isoxaflutole II. Characterization of the Inhibition of Carrot 4-Hydroxyphenylpyruvate Dioxygenase by the Diketonitrile Derivative of Isoxaflutole

Abstract Isoxaflutole (5-cyclopropylisoxazol-4-yl 2-mesyl-4-trifluromethylphenyl ketone) is a novel herbicide for broadleaf and grass weed control in corn and sugarcane which acts by inhibiting the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD). In plants and soil, isoxaflutole is rapidly converted to a diketonitrile derivative (DKN) which is the active herbicide principle. The kinetics of inhibition of carrot HPPDin vitroby the DKN showed that it is a potent tight-binding inhibitor (IC50value 4.9 ± 0.2 nM) exhibiting a time-dependent interaction with the enzyme in its ferrous state. Additional investigations provided evidence that the DKN is a competitive inhibitor that rapidly inactivates the enzyme (with a constant rate of association of 0.2 ± 0.004 μM−1s−1) by forming a reversible complex that releases slowly the inhibitor in an unmodified form. The decarboxylation coupled with reduction of molecular oxygen is generally accepted as the first enzymatic event of the HPPD-catalyzed reaction which occurs as 4-hyroxyphenylpyruvate binds to the internal iron of proteinviaits ketoacid function. The DKN of isoxaflutole presents a β-(1,3)-diketone moiety, a delocalized π system which can mimic the ketoacid functionality of the substrate and which is also well known for its iron-chelating properties. Since this inhibitor competes with the substrate for binding, it is highly probable that it chelates the ferrous iron in the active site strongly by forming a stable ion-dipole charge transfer complex that resembles the initial substrate-iron complex or an early reaction intermediate. The slow release of the inhibitor in an unmodified form also suggests that the molecular oxygen activation due to ferrous iron generating a powerful oxidant as the inhibitor-enzyme complex forms is probably not occurring.

更新日期：1998-11-01

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