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Review
. 2021 Mar 15:214:113233.
doi: 10.1016/j.ejmech.2021.113233. Epub 2021 Jan 30.

Advance of structural modification of nucleosides scaffold

Xia Lin  1 , Chunxian Liang  2 , Lianjia Zou  2 , Yanchun Yin  2 , Jianyi Wang  3 , Dandan Chen  2 , Weisen Lan  4
Affiliations
Review

Advance of structural modification of nucleosides scaffold

Xia Lin et al. Eur J Med Chem. .

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, -CF3, 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.

Keywords: Anti-tumor; Antiviral; Nucleosides scaffold; Prodrugs; Triazoles.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
2′-Modified nucleoside analogues with antiviral activities.
Fig. 2
Fig. 2
2′-Modified nucleoside analogues with anti-tumor activities.
Fig. 3
Fig. 3
3′-Modified nucleoside analogues with anti-tumor activities.
Fig. 4
Fig. 4
2′,3′-Modified nucleoside analogues with antiviral activities.
Fig. 5
Fig. 5
L-type Nucleoside analogue with anti-tumor activity.
Fig. 6
Fig. 6
4′-Site modified nucleoside analogues with antiviral activities.
Fig. 7
Fig. 7
5′-Site modified nucleoside analogues with antiviral activities.
Fig. 8
Fig. 8
5′-Site modified nucleoside analogues with anti-tumor activities.
Fig. 9
Fig. 9
Carbocyclic nucleoside analogues.
Fig. 10
Fig. 10
“PMEA” type acyclic nucleoside analogues.
Fig. 11
Fig. 11
“PMEG” type acyclic nucleoside analogues.
Fig. 12
Fig. 12
Pyrimidine acyclic nucleoside analogues.
Fig. 13
Fig. 13
Purine modified nucleoside analogues with antiviral activities.
Fig. 14
Fig. 14
Purine modified nucleoside analogues with anti-tumor activities.
Fig. 15
Fig. 15
Pyrimidine modified nucleoside analogues with antiviral activities.
Fig. 16
Fig. 16
Pyrimidine modified nucleoside analogues with anti-tumor activities.
Fig. 17
Fig. 17
Ribavirin and its analogues with antiviral activities (black ones)and anti-tumor activities (blue ones).
Fig. 18
Fig. 18
Aryl-modified triazole nucleoside analogues with antiviral activities (black ones) and anti-tumor activities (blue ones).
Fig. 19
Fig. 19
1,2,3-Triazole nucleoside analogues.
Fig. 20
Fig. 20
1,2,3-Triazole nucleoside derivatives with antiviral activities (black ones) and anti-tumor activities (blue ones).
Fig. 21
Fig. 21
Antiviral “double prodrugs”.
Fig. 22
Fig. 22
Anti-tumor “double prodrugs”.
Fig. 23
Fig. 23
Cholesterol conjugated nucleosides.
Fig. 24
Fig. 24
Polyethylene glycol conjugated nucleosides.
Fig. 25
Fig. 25
Fatty acid modified nucleosides.
Fig. 26
Fig. 26
Phospholipid conjugated nucleosides.
See this image and copyright information in PMC

References

    1. Jazayeri A., Falck J., Lukas C., Bartek J., Smith G.C.M., Lukas J., Jackson S.P. ATM-and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat. Cell Biol. 2006;8:37–45. - PubMed
    1. Ewald B., Sampath D., Plunkett W. Nucleoside analogs: molecular mechanisms signaling cell death. Oncogene. 2008;27:6522–6537. - PubMed
    1. Lo1 M.K., Feldmann F., Gary J.M., Jordan R., Bannister R., Cronin J., Patel N.R., Klena1 J.D., Nichol S.T., Cihlar T., Zaki S.R., Feldmann H., Spiropoulou C.F., de Wit E., Remdesivir G.S.- 5734) protects African green monkeys from Nipah virus challenge. Sci. Transl. Med. 2019;11 - PMC - PubMed
    1. Tchesnokov E.P., Feng J.Y., Porter D.P., Götte M. Mechanism of inhibition of Ebola virus RNA-dependent RNA polymerase by Remdesivir. Viruses. 2019;11:e326. - PMC - PubMed
    1. Sheahan T.P., Sims A.C., Leist S.R., Schäfer A., Won J., Brown A.J., Montgomery S.A., Hogg A., Babusis D., Clarke M.O., Spahn J.E., Bauer L., Sellers S., Porter D., Feng J.Y., Cihlar T., Jordan R., Denison M.R., Baric R.S. Comparative therapeutic efficacy of Remdesivir and combination Lopinavir, Ritonavir, and interferon beta against MERS-CoV. Nat. Commun. 2020;11:e222. - PMC - PubMed

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