Design, synthesis, and biological activity evaluation of dihydromyricetin derivatives against SARS-CoV-2-Omicron virus.

IF 5.6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Cong Wu, Qi Jiang, Hui Zhong, Xudong Zhou, Leping Liu, Tong Pan, Chao Liu, Wei Wang, Wenbing Sheng
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引用次数: 0

Abstract

An oxidising and substituting one-pot reaction strategy has been developed to synthesise dihydromyricetin derivatives with the aim of enhancing the inhibitory activity of dihydromyricetin against SARS-CoV-2. Different ω-methoxy-ω-oxeylkyl was introduced in C7-OH site and yielded eight analogs, all of them showed good inhibitory activity against SARS-CoV-2 3CLpro with IC50 values ranging from 0.72 to 2.36 μM. In the Vero E6-cell, compound 3 has a good activity of anti-SARS-CoV-2 virus (Omicron virus BA.5) in the prevention model, with an EC50 of 15.84 μM, and so do compound 10 in the therapeutic model, with an EC50 of 11.52 μM. The results suggest that the introduction of long chain ω-oxeylkyl at C7-OH facilitate the inhibition of viral replication in the therapeutic model, which is consistent with the binding energies predicted from molecular docking conclusions. It implies that dihydromyricetin derivatives have the potential to become effective inhibitors of SARS-CoV-2 Omicron and other viruses.

针对 SARS-CoV-2-Omicron 病毒的二氢杨梅素衍生物的设计、合成和生物活性评价。
为了提高二氢杨梅素对SARS-CoV-2的抑制活性,我们开发了一种氧化和取代的一锅反应策略来合成二氢杨梅素衍生物。在 C7-OH 位点引入了不同的ω-甲氧基-ω-氧烷基,得到了 8 种类似物,它们对 SARS-CoV-2 3CLpro 都表现出良好的抑制活性,IC50 值在 0.72 到 2.36 μM 之间。在 Vero E6 细胞中,化合物 3 在预防模型中具有良好的抗 SARS-CoV-2 病毒(Omicron 病毒 BA.5)活性,EC50 为 15.84 μM;化合物 10 在治疗模型中也具有良好的抗 SARS-CoV-2 病毒活性,EC50 为 11.52 μM。结果表明,在 C7-OH 处引入长链ω-氧烷基有助于抑制治疗模型中的病毒复制,这与分子对接结论预测的结合能是一致的。这意味着二氢杨梅素衍生物有可能成为 SARS-CoV-2 Omicron 和其他病毒的有效抑制剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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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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