N-苯基邻苯二甲酰亚胺作为强效原卟啉原氧化酶抑制剂的设计与合成,Molecules

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N-苯基邻苯二甲酰亚胺作为强效原卟啉原氧化酶抑制剂的设计与合成
Molecules ( IF 4.2 ) Pub Date : 2019-11-29 , DOI: 10.3390/molecules24234363
Wei Gao ₁ , Xiaotian Li ₁ , Da Ren ₁ , Susu Sun ₁ , Jingqian Huo ₁ , Yanen Wang ₁ , Lai Chen ₁ , Jinlin Zhang ₁

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原卟啉原氧化酶 (PPO) 已被确定为最有希望的除草剂发现目标之一。以氟虫嗪为先导物，针对烟草线粒体PPO（mtPPO，PDB：1SEZ）的晶体结构，通过分子对接研究设计了一系列新型邻苯二甲酰亚胺衍生物，随后合成并表征了这些衍生物，并随后对其除草活性进行了研究。评估。除草剂生物测定结果表明，3a(2-(4-bromo-2,6-difluorophenyl)isoindoline-1,3-dione)、3d(methyl 2-(4-chloro-1,3-dioxoisoindolin-2 -yl)-5-氟苯甲酸酯), 3g (4-chloro-2-(5-methylisoxazol-3-yl)isoindoline-1,3-dione), 3j (4-chloro-2-(thiophen-2-ylmethyl) isoindoline-1,3-dione)和3r(2-(4-bromo-2,6-difluorophenyl)-4-fluoroisoindoline-1,3-dione)具有良好的除草活性；其中，3a通过小杯法和芽前和芽后喷雾处理对A.retroflexus和B. campestris表现出优异的除草效果。其功效与商业除草剂氟胺恶嗪、莠去津和氯脲的功效相当。此外，酶活性测定结果表明化合物3a的作用方式涉及对PPO酶的抑制，3a对PPO的抑制活性优于氟虫嗪。这些结果表明我们的分子设计策略有助于开发新的有前途的 PPO 抑制剂。其功效可与商业除草剂氟胺恶嗪、莠去津和氯脲隆的功效相媲美。此外，酶活性测定结果表明化合物3a的作用方式涉及对PPO酶的抑制，3a对PPO的抑制活性优于氟虫嗪。这些结果表明我们的分子设计策略有助于开发新的有前途的 PPO 抑制剂。其功效与商业除草剂氟胺恶嗪、莠去津和氯脲的功效相当。此外，酶活性测定结果表明化合物3a的作用方式涉及对PPO酶的抑制，3a对PPO的抑制活性优于氟虫嗪。这些结果表明我们的分子设计策略有助于开发新的有前途的 PPO 抑制剂。

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Design and Synthesis of N-phenyl Phthalimides as Potent Protoporphyrinogen Oxidase Inhibitors

Protoporphyrinogen oxidase (PPO) has been identified as one of the most promising targets for herbicide discovery. A series of novel phthalimide derivatives were designed by molecular docking studies targeting the crystal structure of mitochondrial PPO from tobacco (mtPPO, PDB: 1SEZ) by using Flumioxazin as a lead, after which the derivatives were synthesized and characterized, and their herbicidal activities were subsequently evaluated. The herbicidal bioassay results showed that compounds such as 3a (2-(4-bromo-2,6-difluorophenyl) isoindoline-1,3-dione), 3d (methyl 2-(4-chloro-1,3-dioxoisoindolin-2-yl)-5-fluorobenzoate), 3g (4-chloro-2-(5-methylisoxazol-3-yl) isoindoline-1,3-dione), 3j (4-chloro-2-(thiophen-2-ylmethyl) isoindoline-1,3-dione) and 3r (2-(4-bromo-2,6-difluorophenyl)-4-fluoroisoindoline-1,3-dione) had good herbicidal activities; among them, 3a showed excellent herbicidal efficacy against A. retroflexus and B. campestris via the small cup method and via pre-emergence and post-emergence spray treatments. The efficacy was comparable to that of the commercial herbicides Flumioxazin, Atrazine, and Chlortoluron. Further, the enzyme activity assay results suggest that the mode of action of compound 3a involves the inhibition of the PPO enzyme, and 3a showed better inhibitory activity against PPO than did Flumioxazin. These results indicate that our molecular design strategy contributes to the development of novel promising PPO inhibitors.

更新日期：2019-11-29

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