Design, synthesis, SAR and molecular docking of novel green niacin-triketone HPPD inhibitor
Design, synthesis, SAR and molecular docking of novel green niacin-triketone HPPD inhibitor
复制标题
新型绿色烟酸三酮HPPD抑制剂的设计、合成、SAR及分子对接
DOI：
10.1016/j.indcrop.2019.05.070
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发表时间：
2019-10-01
影响因子：
5.9
通讯作者：
Ye, Fei
中科院分区：
文献类型：
--
作者：
Fu, Ying;Zhang, Shuai-Qi;Ye, Fei
4-羟苯丙酮酸双加氧酶（Hydroxyphenylpyruvate 1.13.11.27，HPPD）是发现新型漂白除草剂的重要靶标。为了寻找具有良好除草活性和作物选择性的新型绿色三酮HPPD抑制剂，以天然产物leptospermone为模板化合物，烟酸为生物电子等排体，设计合成了一系列新型取代烟酸三酮衍生物。部分目标化合物在体外表现出较强的拟南芥HPPD（AtHPPD）抑制活性。尤其是化合物II-1显示出最好的除草活性（IC 50 = 0.262 μ M，AtHPPD），并且在300 g ai/ha的浓度下对玉米是安全的。分子对接结果表明，化合物II-1的三酮部分可与Fe（II）形成双齿配合物，吡啶亚基与Phe 430和Phe 360以pi-pi堆积方式相互作用.本工作表明3-羟基-2-烟酰基环己-2-烯-1-酮可能是开发新型绿色HPPD抑制剂的潜在先导结构。
4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) is a very important target for the discovery of novel bleaching herbicides. In order to discover novel triketone green HPPD inhibitors with excellent herbicidal activity and crop selectivity, the natural product leptospermone was selected as the template compound, and niacin was employed as bioisostere to design and synthesize a series of novel substituted niacin-triketone derivatives. Some of the target compounds showed potent Arabidopsis thaliana HPPD (AtHPPD) inhibitory activity in vitro. Especially compound II-1 displayed the best herbicidal activity (IC50 = 0.262 mu M, AtHPPD), and was safe for Zea mays at concentration of 300 g ai/ha. Molecular docking results indicated that the triketone moiety of compound II-1 could form a bidentate complex with Fe(II), and the pyridine subunit interacted with Phe430 and Phe360 via pi-pi packing. The present work indicated that 3-hydroxy-2-nicotinoylcyclohex-2-en-1-one could be a potential lead structure for developing novel green HPPD inhibitors.