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5′-O-Masked 2′-deoxyadenosine analogues as lead compounds for hepatitis C virus (HCV) therapeutic agents

On the basis of our previous study on antiviral agents against the severe acute respiratory syndrome (SARS) coronavirus, a series of nucleoside analogues whose 5′-hydroxyl groups are masked by various protective groups such as carboxylate, sulfonate, and ether were synthesized and evaluated to devel...

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Detalles Bibliográficos
Autores principales: Ikejiri, Masahiro, Ohshima, Takayuki, Kato, Keizo, Toyama, Masaaki, Murata, Takayuki, Shimotohno, Kunitada, Maruyama, Tokumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125560/
https://www.ncbi.nlm.nih.gov/pubmed/17766124
http://dx.doi.org/10.1016/j.bmc.2007.08.025
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author Ikejiri, Masahiro
Ohshima, Takayuki
Kato, Keizo
Toyama, Masaaki
Murata, Takayuki
Shimotohno, Kunitada
Maruyama, Tokumi
author_facet Ikejiri, Masahiro
Ohshima, Takayuki
Kato, Keizo
Toyama, Masaaki
Murata, Takayuki
Shimotohno, Kunitada
Maruyama, Tokumi
author_sort Ikejiri, Masahiro
collection PubMed
description On the basis of our previous study on antiviral agents against the severe acute respiratory syndrome (SARS) coronavirus, a series of nucleoside analogues whose 5′-hydroxyl groups are masked by various protective groups such as carboxylate, sulfonate, and ether were synthesized and evaluated to develop novel anti-hepatitis C virus (HCV) agents. Among these, several 5′-O-masked analogues of 6-chloropurine-2′-deoxyriboside (e.g., 5′-O-benzoyl, 5′-O-p-methoxybenzoyl, and 5′-O-benzyl analogues) were found to exhibit effective anti-HCV activity. In particular, the 5′-O-benzoyl analogue exhibited the highest potency with an EC(50) of 6.1 μM in a cell-based HCV replicon assay. Since the 5′-O-unmasked analogue (i.e., 6-chloropurine-2′-deoxyriboside) was not sufficiently potent (EC(50) = 47.2 μM), masking of the 5′-hydroxyl group seems to be an effective method for the development of anti-HCV agents. Presently, we hypothesize two roles for the 5′-O-masked analogues: One is the role as an anti-HCV agent by itself, and the other is as a prodrug of its 5′-O-demasked (deprotected) derivative.
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spelling pubmed-71255602020-04-08 5′-O-Masked 2′-deoxyadenosine analogues as lead compounds for hepatitis C virus (HCV) therapeutic agents Ikejiri, Masahiro Ohshima, Takayuki Kato, Keizo Toyama, Masaaki Murata, Takayuki Shimotohno, Kunitada Maruyama, Tokumi Bioorg Med Chem Article On the basis of our previous study on antiviral agents against the severe acute respiratory syndrome (SARS) coronavirus, a series of nucleoside analogues whose 5′-hydroxyl groups are masked by various protective groups such as carboxylate, sulfonate, and ether were synthesized and evaluated to develop novel anti-hepatitis C virus (HCV) agents. Among these, several 5′-O-masked analogues of 6-chloropurine-2′-deoxyriboside (e.g., 5′-O-benzoyl, 5′-O-p-methoxybenzoyl, and 5′-O-benzyl analogues) were found to exhibit effective anti-HCV activity. In particular, the 5′-O-benzoyl analogue exhibited the highest potency with an EC(50) of 6.1 μM in a cell-based HCV replicon assay. Since the 5′-O-unmasked analogue (i.e., 6-chloropurine-2′-deoxyriboside) was not sufficiently potent (EC(50) = 47.2 μM), masking of the 5′-hydroxyl group seems to be an effective method for the development of anti-HCV agents. Presently, we hypothesize two roles for the 5′-O-masked analogues: One is the role as an anti-HCV agent by itself, and the other is as a prodrug of its 5′-O-demasked (deprotected) derivative. Elsevier Ltd. 2007-11-15 2007-08-22 /pmc/articles/PMC7125560/ /pubmed/17766124 http://dx.doi.org/10.1016/j.bmc.2007.08.025 Text en Copyright © 2007 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Ikejiri, Masahiro
Ohshima, Takayuki
Kato, Keizo
Toyama, Masaaki
Murata, Takayuki
Shimotohno, Kunitada
Maruyama, Tokumi
5′-O-Masked 2′-deoxyadenosine analogues as lead compounds for hepatitis C virus (HCV) therapeutic agents
title 5′-O-Masked 2′-deoxyadenosine analogues as lead compounds for hepatitis C virus (HCV) therapeutic agents
title_full 5′-O-Masked 2′-deoxyadenosine analogues as lead compounds for hepatitis C virus (HCV) therapeutic agents
title_fullStr 5′-O-Masked 2′-deoxyadenosine analogues as lead compounds for hepatitis C virus (HCV) therapeutic agents
title_full_unstemmed 5′-O-Masked 2′-deoxyadenosine analogues as lead compounds for hepatitis C virus (HCV) therapeutic agents
title_short 5′-O-Masked 2′-deoxyadenosine analogues as lead compounds for hepatitis C virus (HCV) therapeutic agents
title_sort 5′-o-masked 2′-deoxyadenosine analogues as lead compounds for hepatitis c virus (hcv) therapeutic agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125560/
https://www.ncbi.nlm.nih.gov/pubmed/17766124
http://dx.doi.org/10.1016/j.bmc.2007.08.025
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