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6-氯嘌呤异恶唑啉-碳环单磷酸核苷酸对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的RNA依赖性RNA聚合酶的抑制作用

Inhibition of the RNA-Dependent RNA-Polymerase from SARS-CoV-2 by 6-Chloropurine Isoxazoline-Carbocyclic Monophosphate Nucleotides.

作者信息

Leusciatti Marco, Macchi Beatrice, Marino-Merlo Francesca, Mastino Antonio, Morra Giulia, Quadrelli Paolo

机构信息

Department of Chemistry, University of Pavia, Viale Taramelli 12, 27100 Pavia,Italy.

Department of Chemical Science and Technology, University of Rome Tor Vergata, Via della ricerca scientifica 1, 00133 Roma, Italy.

出版信息

ACS Omega. 2023 Sep 20;8(39):36311-36320. doi: 10.1021/acsomega.3c04918. eCollection 2023 Oct 3.

DOI:10.1021/acsomega.3c04918
PMID:37810686
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10552509/
Abstract

Isoxazoline-carbocyclic monophosphate nucleotides were designed and synthesized through the chemistry of nitrosocarbonyl intermediates and stable anthracenenitrile oxide. Docking and molecular dynamics studies were first conducted for determining the best candidate for polymerase SARS-CoV-2 inhibition. The setup phosphorylation protocol afforded the nucleotides available for the biological tests. Preliminary inhibition and cytotoxicity assays were then performed, and the results showed a moderate activity of the nucleotides accompanied by cytotoxicity.

摘要

异恶唑啉-碳环单磷酸核苷酸是通过亚硝基羰基中间体和稳定的蒽腈氧化物化学方法设计合成的。首先进行对接和分子动力学研究以确定抑制聚合酶SARS-CoV-2的最佳候选物。设定的磷酸化方案提供了可用于生物学测试的核苷酸。然后进行了初步抑制和细胞毒性测定，结果显示核苷酸具有中等活性并伴有细胞毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e78/10552509/c334e5be4129/ao3c04918_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e78/10552509/f760a4c7761b/ao3c04918_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e78/10552509/22b11ef95287/ao3c04918_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e78/10552509/3e0ba9667c04/ao3c04918_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e78/10552509/be9f319c5546/ao3c04918_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e78/10552509/4d541d38e7f6/ao3c04918_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e78/10552509/004244ba7806/ao3c04918_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e78/10552509/63c34fb165da/ao3c04918_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e78/10552509/7110979b2bc9/ao3c04918_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e78/10552509/c334e5be4129/ao3c04918_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e78/10552509/f760a4c7761b/ao3c04918_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e78/10552509/22b11ef95287/ao3c04918_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e78/10552509/3e0ba9667c04/ao3c04918_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e78/10552509/be9f319c5546/ao3c04918_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e78/10552509/4d541d38e7f6/ao3c04918_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e78/10552509/004244ba7806/ao3c04918_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e78/10552509/63c34fb165da/ao3c04918_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e78/10552509/7110979b2bc9/ao3c04918_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e78/10552509/c334e5be4129/ao3c04918_0006.jpg

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