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核苷骨架的结构修饰进展。

Advance of structural modification of nucleosides scaffold.

作者信息

Lin Xia, Liang Chunxian, Zou Lianjia, Yin Yanchun, Wang Jianyi, Chen Dandan, Lan Weisen

机构信息

Medical College, Guangxi University, Nanning, 530004, China; College of Chemistry and Chemical Engineering, Guangxi University, Nanning, 530004, China; Guangxi Medical College, Nanning, 530023, China.

Guangxi Medical College, Nanning, 530023, China.

出版信息

Eur J Med Chem. 2021 Mar 15;214:113233. doi: 10.1016/j.ejmech.2021.113233. Epub 2021 Jan 30.

DOI:10.1016/j.ejmech.2021.113233
PMID:33550179
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7995807/
Abstract

With Remdesivir being approved by FDA as a drug for the treatment of Corona Virus Disease 2019 (COVID-19), nucleoside drugs have once again received widespread attention in the medical community. Herein, we summarized modification of traditional nucleoside framework (sugar + base), traizole nucleosides, nucleoside analogues assembled by other drugs, macromolecule-modified nucleosides, and their bioactivity rules. 2'-"Ara"-substituted by -F or -CN group, and 3'-"ara" substituted by acetylenyl group can greatly influence their anti-tumor activities. Dideoxy dehydrogenation of 2',3'-sites can enhance antiviral efficiencies. Acyclic nucleosides and L-type nucleosides mainly represented antiviral capabilities. 5-F Substituted uracil analogues exihibit anti-tumor effects, and the substrates substituted by -I, -CF, bromovinyl group usually show antiviral activities. The sugar coupled with 1-N of triazolid usually displays anti-tumor efficiencies, while the sugar coupled with 2-N of triazolid mainly represents antiviral activities. The nucleoside analogues assembled by cholesterol, polyethylene glycol, fatty acid and phospholipid would improve their bioavailabilities and bioactivities, or reduce their toxicities.

摘要

随着瑞德西韦被美国食品药品监督管理局（FDA）批准为治疗2019冠状病毒病（COVID-19）的药物，核苷类药物再次受到医学界的广泛关注。在此，我们总结了传统核苷骨架（糖 + 碱基）的修饰、三唑核苷、由其他药物组装的核苷类似物、大分子修饰的核苷及其生物活性规律。2'-位被-F或-CN基团取代的“Ara”，以及3'-位被乙炔基取代的“ara”，可极大地影响它们的抗肿瘤活性。2'、3'-位的双脱氧脱氢可提高抗病毒效率。无环核苷和L型核苷主要表现出抗病毒能力。5-F取代的尿嘧啶类似物具有抗肿瘤作用，而被-I、-CF、溴乙烯基取代的底物通常表现出抗病毒活性。与三唑烷的1-N相连的糖通常具有抗肿瘤效率，而与三唑烷的2-N相连的糖主要表现出抗病毒活性。由胆固醇、聚乙二醇、脂肪酸和磷脂组装的核苷类似物可提高它们的生物利用度和生物活性，或降低它们的毒性。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/0ca68d41b9f7/gr8_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/46f0ebccbde0/gr9_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/a0faf639be4e/gr10_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/be860de66f22/gr11_lrg.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/bbf63788a22d/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/45b7740e101c/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/56be829f80ef/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/53e6faa259ca/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/1fd2cebe87c0/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/0ca68d41b9f7/gr8_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/46f0ebccbde0/gr9_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/a0faf639be4e/gr10_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/be860de66f22/gr11_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/1db73634b110/gr12_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/00f802d9e560/gr13_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/52aae15910d5/gr14_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/5b33cd00955e/gr15_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/48a7f8ffb287/gr16_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/32784f37588e/gr17_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/2e6c6e340335/gr18_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/e73e29fae4d5/gr19_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/971d5849a7c8/gr20_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/efbc5cfaa52b/gr21_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/cd7d5dbc4363/gr22_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/2c4f28e176fe/gr23_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d1/7995807/27f288f6881b/gr24_lrg.jpg
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