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基于异吲哚片段与(+)-莰酮或(-)-胡椒酮腙的共轭物的汉坦病毒新类抑制剂

New class of hantaan virus inhibitors based on conjugation of the isoindole fragment to (+)-camphor or (-)-fenchone hydrazonesv.

机构信息

N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, Lavrent'ev av., 9, Novosibirsk 630090, Russia.

State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, Koltsovo, Novosibirsk Region 630559, Russia.

出版信息

Bioorg Med Chem Lett. 2021 May 15;40:127926. doi: 10.1016/j.bmcl.2021.127926. Epub 2021 Mar 9.

Abstract

This work presents the design and synthesis of camphor, fenchone, and norcamphor N-acylhydrazone derivatives as a new class of inhibitors of the Hantaan virus, which causes haemorrhagic fever with renal syndrome (HFRS). A cytopathic model was developed for testing chemotherapeutics against the Hantaan virus, strain 76-118. In addition, a study of the antiviral activity was carried out using a pseudoviral system. It was found that the hit compound possesses significant activity (IC = 7.6 ± 2 µM) along with low toxicity (CC > 1000 µM). Using molecular docking procedures, the binding with Hantavirus nucleoprotein was evaluated and the correlation between the structure of the synthesised compounds and the antiviral activity was established.

摘要

本工作设计并合成了莰酮、葑酮和降蒈酮 N-酰腙衍生物,作为汉坦病毒(引起肾综合征出血热的病原体)的新型抑制剂。建立了细胞病变模型来测试汉坦病毒 76-118 株的化学治疗药物。此外,还使用假病毒系统研究了抗病毒活性。结果发现,该先导化合物具有显著的活性(IC = 7.6 ± 2 μM)和低毒性(CC > 1000 μM)。通过分子对接程序评估了与汉坦病毒核蛋白的结合,并建立了所合成化合物的结构与抗病毒活性之间的相关性。

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