作为 SARS-CoV-2 Mpro 抑制剂的二硫代氨基甲酸酯衍生物的设计、合成和生物学评价。

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL Bioorganic & Medicinal Chemistry Letters Pub Date : 2024-10-30 DOI:10.1016/j.bmcl.2024.130011

Jin-Qi Peng , Ya-Qi Xiao , Jiao Long , Shuang-Shuang Zhang , Yuan-Yuan Zhu , Shuang-Xi Gu

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引用次数: 0

摘要

SARS-CoV-2 不断变异、传播，影响着公众健康和日常生活。主要蛋白酶（Mpro）对 SARS-CoV-2 的复制和成熟至关重要，由于其高度保守性和在人类中缺乏同源蛋白酶，它成为抗冠状病毒药物发现和开发的理想靶点。在此，我们设计并合成了一系列二硫代氨基甲酸盐衍生物，作为强效的 SARS-CoV-2 Mpro 抑制剂。值得注意的是，化合物 L2 对 SARS-CoV-2 Mpro 的 IC50 值为 9.1 ± 2.0 nM，突显了其作为抗冠状病毒治疗候选药物的潜力，并证明了进一步研究和开发的合理性。

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Design, synthesis, and biological evaluation of dithiocarbamate derivatives as SARS-CoV-2 Mpro inhibitors

SARS-CoV-2 continues to mutate, spread, and impact public health and daily life. The main protease (M^pro) is essential for the replication and maturation of SARS-CoV-2, making it an ideal target for anti-coronaviral drug discovery and development due to its high conservation and lack of homologous proteases in humans. Herein, we designed and synthesized a series of dithiocarbamate derivatives as potent SARS-CoV-2 M^pro inhibitors. Notably, compound L2 exhibited an IC₅₀ value of 9.1 ± 2.0 nM against SARS-CoV-2 M^pro, underscoring its potential as a promising candidate for anti-coronaviral therapy and justifying further research and development.

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来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.