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首例含磺酰胺基咪唑并[1,2-a]吡啶啉杂环化合物作为抗病毒药物的发现。

First Discovery of Imidazo[1,2-]pyridine Mesoionic Compounds Incorporating a Sulfonamide Moiety as Antiviral Agents.

机构信息

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for Research and Development of Fine Chemicals, Guizhou University, Guiyang, Guizhou 550025, People's Republic of China.

出版信息

J Agric Food Chem. 2022 Jun 22;70(24):7375-7386. doi: 10.1021/acs.jafc.2c01813. Epub 2022 Jun 8.

Abstract

The applications of mesoionic compounds and their analogues as agents against plant viruses remain unexplored. This was the first evaluation of the antiviral activities of mesoionic compounds on this issue. Our study involved the design and synthesis of a series of novel imidazo[1,2-]pyridine mesoionic compounds containing a sulfonamide moiety and the assessment of their antiviral activities against (PVY). Compound was assessed on the basis of three-dimensional quantitative structure-activity relationship (3D-QSAR) model analysis and displayed good curative, protective, and inactivating activity effects against PVY at 500 mg/L, up to 51.0, 62.0, and 82.1%, respectively, which were higher than those of commercial ningnanmycin (NNM, at 47.2, 50.1, and 81.4%). Significantly, defensive enzyme activities and proteomics results showed that compound could enhance the defense response by activating the activity of defense enzymes, inducing the glycolysis/gluconeogenesis pathway of tobacco to resist PVY infection. Therefore, our study indicates that compound could be applied as a potential viral inhibitor.

摘要

尚未探索将杂环化合物及其类似物作为抗植物病毒剂的应用。这是首次评估杂环化合物在该问题上的抗病毒活性。我们的研究涉及设计和合成一系列含有磺酰胺部分的新型咪唑并[1,2-]吡啶杂环化合物,并评估它们对 (PVY)的抗病毒活性。基于三维定量构效关系(3D-QSAR)模型分析,评估了化合物 ,并显示出在 500mg/L 下对 PVY 具有良好的治疗、保护和灭活活性作用,分别高达 51.0、62.0 和 82.1%,高于商业宁南霉素(NNM,分别为 47.2、50.1 和 81.4%)。值得注意的是,防御酶活性和蛋白质组学结果表明,化合物 可以通过激活防御酶的活性,诱导烟草糖酵解/糖异生途径来抵抗 PVY 感染,从而增强防御反应。因此,我们的研究表明化合物 可用作潜在的病毒抑制剂。

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