新型3CLpro抗SARS-CoV-2抑制剂硫酰胺连接螺吡咯烷衍生物的设计、合成和生物学评价

IF 3.3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry Pub Date : 2025-05-14 DOI:10.1016/j.bmc.2025.118239

Samuel Desta Guma , Kang Song , Haiguo Sun , Lei Yang , Zhaoyin Zhou , Jin Suo , Emmanuel Mintah Bonku , Wei Zheng , Guanghui Tian , Xiangrui Jiang , Qiumeng Zhang , Yan Zhang , Jingshan Shen

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引用次数: 0

摘要

合成了一系列硫酰胺连接的螺吡咯烷衍生物，并对其抗sars - cov - 23clpro进行了评价。其中9g对3CLpro具有显著的抑制作用（IC50 = 35 nM），超过了已批准的抗病毒药物nirmatrelvir （IC50 = 54 nM）。在Huh7细胞中对HCoV-OC43的细胞实验中，9g表现出显著的抗病毒效果（EC50 = 0.52 μM）和低细胞毒性(CC50 >；10μM)。此外，9g表现出与尼马特利韦相当的药代动力学特征，使其成为进一步开发的有希望的候选药物。

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Design, synthesis, and biological evaluation of thioamide-linked spiropyrrolidine derivatives as novel 3CLpro inhibitors against SARS-CoV-2

A series of thioamide-linked spiropyrrolidine derivatives were synthesized and evaluated against SARS-CoV-2 3CL^pro. Among these compounds, 9g demonstrated remarkable inhibition of 3CL^pro (IC₅₀ = 35 nM), surpassing the inhibitory potency of the approved antiviral drug nirmatrelvir (IC₅₀ = 54 nM). In cellular assays against HCoV-OC43 in Huh7 cells, 9g exhibited significant antiviral efficacy (EC₅₀ = 0.52 μM) and low cytotoxicity (CC₅₀ > 10 μM). Furthermore, 9g exhibited pharmacokinetic profiles comparable to that of nirmatrelvir, making it a promising candidate for further development.

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来源期刊

Bioorganic & Medicinal Chemistry 医学-生化与分子生物学

CiteScore

6.80

自引率

2.90%

发文量

413

审稿时长

17 days

期刊介绍： Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.