SARS-CoV-2 3CLpro抑制剂的设计、合成及分子对接研究
Design, Synthesis and Molecular Docking of SARS-CoV-2 3CLpro Inhibitors
DOI: 10.12677/HJMCe.2022.104037, PDF,    科研立项经费支持
作者: 黄 云, 司小宝, 何昕玙, 赵慧宇, 亓振凯, 聂木子*：武汉工程大学，化工与制药学院，湖北 武汉
关键词: SARS-CoV-2抑制剂；生物电子等排体原理；合成；分子对接；SARS-CoV-2 Inhibitors； Bioisosterism； Synthesis； Molecular Docking
摘要: 本研究以结构简单且活性优异的SARS-CoV-2 3CLpro抑制剂1为先导化合物，基于生物电子等排体原理设计了一系列新型吲哚苯酯衍生物。所有化合物均经一步酯化反应合成得到，利用1H NMR、13C NMR和HR-MS确定了其结构。分子对接结果显示部分化合物的打分高于先导化合物，这表明吲哚苯酯衍生物有望被开发为新型SARS-CoV-2 3CLpro抑制剂。
Abstract: In this study, SARS-CoV-2 3CLpro inhibitor 1 with a simple structure and potent antiviral activity was used as the lead compound to design a novel series of indolyl phenyl ester derivatives based on bi-oisosterism. All compounds were synthesized by one-step esterification, and their structures were characterized by 1H NMR, 13C NMR and HR-MS. Molecular docking results showed that some compounds displayed higher scores than the lead compound, indicating that indolyl phenyl ester derivatives could be developed as a novel SARS-CoV-2 3CLpro inhibitors.
文章引用：黄云, 司小宝, 何昕玙, 赵慧宇, 亓振凯, 聂木子. SARS-CoV-2 3CLpro抑制剂的设计、合成及分子对接研究[J]. 药物化学, 2022, 10(4): 352-357. https://doi.org/10.12677/HJMCe.2022.104037

参考文献

[1] Joshee, W.J. and Prescott, H.C. (2020) What Is COVID-19? The Journal of the American Medical Association, 324, 816. [Google Scholar] [CrossRef] [PubMed]
[2] Lamers, M.M. and Haagmans, B.L. (2022) SARS-CoV-2 Patho-genesis. Nature Reviews Microbiology, 20, 270-284. [Google Scholar] [CrossRef] [PubMed]
[3] Zhang, X.T., Zhang, H. and He, X. (2022) SARS-CoV-2 Omi-cron: A New Challenge for Pandemic and Vaccine. Signal Transduction and Targeted Therapy, 7, Article No. 211. [Google Scholar] [CrossRef] [PubMed]
[4] Yan, W.Z., Zheng, Y.H., Zeng, X.T., He, B. and Cheng, W. (2022) Structural Biology of SARS-CoV-2: Open the Door for Novel Therapies. Signal Transduction and Targeted Therapy, 7, Article No. 26. [Google Scholar] [CrossRef] [PubMed]
[5] Zhong, W. Brancaleone, V. and Sultana, J. (2022) Editorial: The Mechanisms of Action of Anti-SARS-CoV-2 Drugs. Frontiers in Pharmacology, 13, Article ID: 894310. [Google Scholar] [CrossRef] [PubMed]
[6] Mengist, H.M., Fan, X.J. and Jin, T.C. (2020) Designing of Im-proved Drugs for COVID-19: Crystal Structure of SARS-CoV-2 Main Protease Mpro. Signal Transduction and Target-ed Therapy, 5, Article No. 67. [Google Scholar] [CrossRef] [PubMed]
[7] Chen, Y., Wang, G. and Ouyang, L. (2020) Promising Inhibitors Targeting Mpro: An Ideal Strategy for Anti-SARS-CoV-2 Drug Discovery. Signal Transduction and Targeted Therapy, 5, Article No. 173. [Google Scholar] [CrossRef] [PubMed]
[8] Ghosh, A.K., Raghavaiah, J., Shahabi, D., Yadav, M., Anson, B.J., Lendy, E.K., Hattori, S.I., Higashi-Kuwata, N., Mitsuya, H. and Mesecar, A.D. (2021) Indole Chloropyridinyl Es-ter-Derived SARS-CoV-2 3CLpro Inhibitors: Enzyme Inhibition, Antiviral Efficacy, Structure-Activity Relationship, and X-ray Structural Studies. Journal of Medicinal Chemistry, 64, 14702-14714. [Google Scholar] [CrossRef] [PubMed]
[9] Zhou, J., Saha, A., Huang, Z.W. and Warshel, A. (2022) Fast and Effective Prediction of the Absolute Binding Free Energies of Covalent Inhibitors of SARS-CoV-2 Main Protease and 20S Proteasome. Journal of the American Chemical Society, 144, 7568-7572. [Google Scholar] [CrossRef] [PubMed]
[10] Subbaiah, M.A.M. and Meanwell, N.A. (2021) Bioisosteres of the Phenyl Ring: Recent Strategic Applications in Lead Optimization and Drug Design. Journal of Medicinal Chemistry, 64, 14046-14128. [Google Scholar] [CrossRef] [PubMed]