核苷类抗病毒药物的研究进展
Research Progress in Nucleoside Antiviral Drugs
DOI: 10.12677/HJMCe.2023.113018, PDF,    科研立项经费支持
作者: 王梦瑶, 万 坤, 张 磊*:浙江师范大学化学与材料学院,浙江 金华;曹凌峰:浙江合糖科技有限公司,浙江 金华
关键词: 抗病毒药物核苷类似物抗病毒生物活性Antiviral Drugs Nucleoside Analogue Antiviral Biological Activity
摘要: 核苷类似物是在临床上广泛使用的一类抗病毒和抗肿瘤药物,在特异性治疗以及广谱抗病毒领域都发挥着至关重要的作用。但在临床使用过程中出现的耐药性、毒性和二重感染等问题给该类药物的发展带来挑战。研究发现通过化学修饰可以影响核苷的抗病毒效力、安全性和耐药性。本文概述了以传统核苷类化合物的结构为基础,从碱基、糖环、磷酸基及糖苷键等几个方面进行结构修饰的研究进展,为进一步开发高抗病毒活性核苷类似物提供借鉴。
Abstract: Modified nucleosides are a major class of anti-virus and anti-tumor drugs, which are widely used in the clinic. However, issues including the emergence of drug resistance, toxicity and superinfection have posed new challenges for nucleoside-based antiviral drug discovery. Many research found that chemical manipulation could impact the antiviral potency, safety, and drug resistance of nucleosides. This article provides an overview of modification of traditional nucleoside framework in order to provide reference for further research and development of highly antiviral nucleoside analogues.
文章引用:王梦瑶, 曹凌峰, 万坤, 张磊. 核苷类抗病毒药物的研究进展[J]. 药物化学, 2023, 11(3): 139-147. https://doi.org/10.12677/HJMCe.2023.113018

参考文献

[1] Kausar, S., Khan, S.F., Ur Rehman, M.I.M., et al. (2021) A Review: Mechanism of Action of Antiviral Drugs. Interna-tional Journal of Immunopathology and Pharmacology, 35, Article ID: 20587384211002621. [Google Scholar] [CrossRef] [PubMed]
[2] Quan, D.J. and Peters, M.G. (2004) Antiviral Therapy: Nucleo-tide and Nucleoside Analoga. Clinics in Liver Disease, 8, 371-385. [Google Scholar] [CrossRef] [PubMed]
[3] Lin, X., Liang, C., Zou, L., et al. (2021) Advance of Structural Modification of Nucleosides Scaffold. European Journal of Medicinal Chemistry, 214, Article ID: 113233. [Google Scholar] [CrossRef] [PubMed]
[4] Peter, H.L., Ku, T.C. and Seley-Radtke, K.L. (2015) Flexibility as a Strategy in Nucleoside Antiviral Drug Design. Current Medicinal Chemistry, 22, 3910-3921. [Google Scholar] [CrossRef] [PubMed]
[5] Prusoff, W.H. (1959) Synthesis and Biological Activi-ties of Iododeoxyuridine, an Analog of Thymidine. Biochimica et Biophysica Acta, 32, 295-296. [Google Scholar] [CrossRef] [PubMed]
[6] De Clercq, E. (2010) Historical Perspectives in the Develop-ment of Antiviral Agents aganist Poxviruses. Viruses, 2, 1322-1339. [Google Scholar] [CrossRef] [PubMed]
[7] Bridges, C.G., Ahmed, S.P., Sunkara, P.S., McCarthy, J.R. and Tyms, A.S. (1995) The Ribonucleotide Reductase Inhibitor (E)-2’-Fluoromethylene-2’-Deoxycytidine: A Potential Topical Therapy for Herpes Simplex Virus Infection. Antiviral Research, 27, 325-334. [Google Scholar] [CrossRef
[8] De Clercq, E., Descamps, J., De Somer, P., et al. (1979) (E)-5-(2-Bromovinyl)-2’-Deoxyuridine: A Potent and Selective Anti-Herpes Agent. Proceedings of the National Acade-my of Sciences of the United States of America, 76, 2947-2951. [Google Scholar] [CrossRef] [PubMed]
[9] Staschke, K.A., Colacino, J.M., Mabry, T.E. and Jones, C.D. (1994) The in Vitro Anti-Hepatitis B Virus Activity of FIAU[1-(2’-Deoxy-2’-Fluoro-1-β-D-Arabinofuranosyl-5-Iodo) Uracil] Is Selective, Reversible, and Determined, at Least in Part, by the Host Cell. Antiviral Research, 23, 45-61. [Google Scholar] [CrossRef] [PubMed]
[10] Mian, A.M. and Khwaja, T.A. (1983) Synthesis and Anti-tumor Activity of 2-Deoxyribofuranosides of 3-Deazaguanine. Journal of Medicinal Chemistry, 26, 286-291. [Google Scholar] [CrossRef] [PubMed]
[11] Chang, H.-W., Wang, H.-C., Chen, C.-Y., et al. (2014) 5-Azacytidine Induces Anokis, Inhibits Mammosphere Formation and Reduces Metalloproteinase 9 Activity in MCF-7 Human Breast Cancer Cells. Molecules, 19, 3149-3159. [Google Scholar] [CrossRef] [PubMed]
[12] Zhou, C.-H. and Wang, Y. (2012) Recent Researches in Triazole Compounds as Medical Drugs. Current Medicinal Chemistry, 19, 239-280. [Google Scholar] [CrossRef] [PubMed]
[13] Sabat, N., Migianu-Griffoni, E., Tudela, T., et al. (2020) Syn-thesis and Antitumor Activities Investigation of a C-Nucleoside Analogue of Ribavirin. European Journal of Medicinal Chemistry, 188, Article ID: 112009. [Google Scholar] [CrossRef] [PubMed]
[14] Dan Do, T.N., Donckers, K., Vangeel, L., et al. (2021) A Ro-bust SARA-CoV-2 Replication Model in Primary Human Epithelial Cells at the Air Liquid Interface to Assess Antiviral Agents. Antiviral Research, 192, Article ID: 105122. [Google Scholar] [CrossRef] [PubMed]
[15] Xie, Y., Yin, W., Zhang, Y., et al. (2021) Design and Devel-opment of an Oral Remdesivir Derivative VV116 against SARS-CoV-2. Cell Research, 31, 1212-1214. [Google Scholar] [CrossRef] [PubMed]
[16] Tosh, D.K., Janowsky, A., Eshleman, A.J., et al. (2017) Scaf-fold Repurposing of Nucleosides (Adenosine Receptor Agonists): Ehhanced Activity at the Humann Dopamine and Nerepinephrine Sodium Symporters. Journal of Medicinal Chemistry, 60, 3109-3123. [Google Scholar] [CrossRef] [PubMed]
[17] Suzuki, M., Okuda, T. and Shiraki, K. (2006) Synergistic An-tiviral Activity of Acyclovir and Vidarabine against Herps Simplex Virus Types 1 and 2 and Varicella-Zoster Virus. An-tiviral Research, 72, 157-161. [Google Scholar] [CrossRef] [PubMed]
[18] Müller, H., Gabrielli, V., Agoglitta, O. and Holl, R. (2016) Chiral Pool Synthesis and Biological Evaluation of C-Furanosidic and Acyclic LpxC Inhibitors. European Journal of Medicinal Chemistry, 110, 340-375. [Google Scholar] [CrossRef] [PubMed]
[19] Costanzi, S., Lambertucci, C., Portino, F.R., et al. (2005) Ring Opening Reactions: Synthesis of AICAR Analogs as Potential Antimetabolite Agents. Nucleosides, Nucleotides & Nu-cleic Acids, 24, 415-418. [Google Scholar] [CrossRef
[20] Mikhailopulo, I.A., Poopeiko, N.E., Pricota, T.I., et al. (1991) Syn-thesis and Antiviral and Cytostatic Properties of 3’-Deoxy-3’-Fluoro- and 2’-Azido-3’-Fluoro-2’,3’-Dedeoxy-D-Ribofuranosides of Natural Heterocyclic Bases. Journal of Medicinal Chemistry, 34, 2195-2202. [Google Scholar] [CrossRef] [PubMed]
[21] Choi, Y., George, C., Comin, M.J., et al. (2003) A Conformationally Locked Analogue of the Anti-HIV Agent Stavudine. An Important Correlation between Pseudorotation and Maximum Amplitude. Journal of Medicinal Chemistry, 46, 3292-3299. [Google Scholar] [CrossRef] [PubMed]
[22] Smith, R.A., Gottlieb, G.S., Anderson, D.J., Pyrak, C.L. and Preston, B.D. (2008) Human Immunodeficiency Virus Types 1 and 2 Exhibit Comparable Sensitivities to Zidovudine and Other Nucleoside Analog Inhibitors in Vitro. Antimicrobial Agents and Chemotherapy, 52, 329-332. [Google Scholar] [CrossRef
[23] Chang, J. (2022) 4’-Modified Nucleosides for Antiviral Drug Dis-covery: Achievements and Perspectives. Accounts of Chemical Research, 55, 565-578. [Google Scholar] [CrossRef] [PubMed]
[24] Bianco, A., Passacantilli, P. and Righi, G. (1988) Improved Procedure for the Reduction of Esters of Alcohols by Sodium Borohydride. Synthetic Communications, 18, 1765-1771. [Google Scholar] [CrossRef
[25] Parang, K., El-Sayed, N.S., Kazeminy, A. and Tiwari, R.K. (2020) Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs against Human Coronavirus 229E (HcoV-229E). Molecules, 25, 2343-2350. [Google Scholar] [CrossRef] [PubMed]
[26] Magg, H., Rydzewski, R.M., McRoberts, M.J., et al. (1992) Synthesis and Anti-HIV Activity of 4’-Azido- and 4’-Methoxynucleosides. Journal of Medicinal Chemistry, 35, 1440-1451. [Google Scholar] [CrossRef] [PubMed]
[27] Houston, D.M., Dolence, E.K., Keller, B.T., et al. (1985) Potential Inhibitors of S-Adenosylmethionine-Dependent Methyltransferases. 9. 2’,3’-Dialdehyde Derivatives of Carbo-cyclic Purine Nucleosides as Inhibitors of S-Adenosyl- homocysteine Hydrolase. Journal of Medicinal Chemistry, 28, 471-477. [Google Scholar] [CrossRef] [PubMed]
[28] Jordheim, L.P., Durantel, D., Zoulim, F. and Dumontet, C. (2013) Advances in the Development of Nucleoside and Nucleotide Analogies for Cancer and Viral Diseases. Nature Reviews Drug Discovery, 12, 447-464. [Google Scholar] [CrossRef] [PubMed]
[29] Harnden, M.R., Jarvest, R.L., Bacon, T.H. and Boyd, M.R. (1987) Synthesis and Antiviral Activity of 9-[4-Hy- droxy-3-(Hydroxymethyl)but-1-yl]Purines. Journal of Medicinal Chemistry, 30, 1636-1642. [Google Scholar] [CrossRef] [PubMed]
[30] Štambaský, J., Hocek, M. and Kocovský, P. (2009) C-Nucleosides: Synthetic Strategies and Biological Applications. Chemical Reviews, 109, 6729-6764. [Google Scholar] [CrossRef] [PubMed]
[31] Chen, M. and Witte, C.-P. (2020) A Kinase and a Glycosylase Catabolize Pseudouridine in the Peroxisome to Prevent Toxic Pseudouridine Monophosphate Accumulation. The Plant Cell, 32, 722-739. [Google Scholar] [CrossRef] [PubMed]
[32] Kan, G.Y., Wang, Z.Y., Sheng, C.S., et al. (2021) Dual Inhibi-tion of DKC1 and MEK1/2 Synergistically Restrains the Growth of Colorectal Cancer Cells. Advanced Science, 8, Article ID: 2004344. [Google Scholar] [CrossRef] [PubMed]
[33] Carrasco, L. and Váquez, D. (1984) Molecular Bases for the Action and Selectivity of Nucleoside Antibiotica. Medicinal Research Reviews, 4, 471-512. [Google Scholar] [CrossRef] [PubMed]
[34] Kicska, G.A., Long, L., Hörig, H, et al. (2001) Immucillin H, a Powerful Transition-State Analog Inhibitor of Purine Nucleoside Phosphorylase, Selectively Inhibits Human T Lym-phocytes. Proceedings of the National Academy of Sciences of the United States of America, 98, 4593-4598. [Google Scholar] [CrossRef] [PubMed]