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Synthesis and Evaluation of Halogenated 5‑(2-Hydroxyphenyl)pyrazoles as Pseudilin Analogues Targeting the Enzyme IspD in the Methylerythritol Phosphate Pathway
journal contribution
posted on 2020-02-28, 21:33 authored by Jili Wang, Yaqing Zhou, Xiuwen Wang, Lixia Duan, Jiang Duan, Weiguo Li, Aidong ZhangThis work reports halogenated 5-(2-hydroxyphenyl)pyrazoles
as pseudilin
analogues with the potential to target the enzyme IspD in the methylerythritol
phosphate (MEP) pathway. Such analogues were designed using the bioisosteric
replacement of the pseudilin core structure and synthesized via an
efficient three-step route. With AtIspD-based screening
and pre- and post-emergence herbicidal tests, these compounds were
demonstrated to have considerable activities against AtIspD, with IC50 up to 3.27 μM, and against model
plants rape and barnyard grass, with moderate to excellent activities.
At a rate of 150 g/ha in the greenhouse test, three compounds exhibited
higher or comparable herbicidal activities than pseudilin. Molecular
docking of representative compounds into the allosteric site of AtIspD revealed a binding mode similar to that of pseudilin.
The established bioisosterism and synthesis method in this work may
serve as an important tool for the development of new herbicides and
antimicrobials targeting IspD in the MEP pathway.
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IspD-based screeningpseudilin analoguesEnzyme IspDSuch analoguesallosteric sitebioisosteric replacementwork reportsbinding modegreenhouse testMEP pathwayenzyme IspDbarnyard grassmethylerythritol phosphateMolecular docking3.27 μ MMethylerythritol Phosphate Pathwaysynthesis methodIC 50Pseudilin Analogues Targetingpost-emergence herbicidal testsrepresentative compoundspseudilin core structureherbicidal activitiesmodel plants rape
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