探索具有良好抗 SARS-CoV-2 活性的 N-邻苯二甲酰亚胺连接的 1,2,3-三唑类似物:合成、生物筛选和分子建模研究。

IF 5.6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ateyatallah Aljuhani, Mosa Alsehli, Mohamed A Seleem, Shaya Y Alraqa, Hany E A Ahmed, Nadjet Rezki, Mohamed R Aouad
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引用次数: 0

摘要

本研究设计、合成了一个与 1,4-二取代-1,2,3-三唑相连的邻苯二甲酰亚胺席夫碱库,并通过不同的光谱分析对其进行了表征。以 Vero 细胞为培养基,对所有类似物进行了体外试验,检测它们对不同浓度 COVID-19 病毒的抗病毒活性。数据显示,这些衍生物中的大多数都具有很强的细胞抗 COVID-19 活性,在两种不同浓度下可阻止 90% 以上的病毒生长,对 Vero 细胞无细胞毒性或细胞毒性很弱。此外,还对所有类似物进行了针对该酶的体外检测,结果显示其中两种类似物的 IC50 数据为 90 µM 抑制活性。为了分析它们的抗病毒机理,我们进行了广泛的分子对接模拟,发现它们在 Mpro 蛋白酶内有适当的非共价相互作用。最后,我们还发现了两种可逆抑制剂,即 COOH 和 F 取代的类似物,它们可能是有希望进一步开发的候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exploring of N-phthalimide-linked 1,2,3-triazole analogues with promising -anti-SARS-CoV-2 activity: synthesis, biological screening, and molecular modelling studies.

In this study, a library of phthalimide Schiff base linked to 1,4-disubstituted-1,2,3-triazoles was designed, synthesised, and characterised by different spectral analyses. All analogues have been introduced for in vitro assay of their antiviral activity against COVID-19 virus using Vero cell as incubator with different concentrations. The data revealed most of these derivatives showed potent cellular anti-COVID-19 activity and prevent viral growth by more than 90% at two different concentrations with no or weak cytotoxic effect on Vero cells. Furthermore, in vitro assay was done against this enzyme for all analogues and the results showed two of them have IC50 data by 90 µM inhibitory activity. An extensive molecular docking simulation was run to analyse their antiviral mechanism that found the proper non-covalent interaction within the Mpro protease enzyme. Finally, we profiled two reversible inhibitors, COOH and F substituted analogues that might be promising drug candidates for further development have been discovered.

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来源期刊
CiteScore
10.30
自引率
10.70%
发文量
195
审稿时长
4-8 weeks
期刊介绍: Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents. Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research. The journal’s focus includes current developments in: Enzymology; Cell biology; Chemical biology; Microbiology; Physiology; Pharmacology leading to drug design; Molecular recognition processes; Distribution and metabolism of biologically active compounds.
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