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Acyclic nucleoside thiophosphonates as potent inhibitors of HIV and HBV replication

9-[2-(Thiophosphonomethoxy)ethyl]adenine 3 and (R)-9-[2-(Thiophosphonomethoxy)propyl]adenine 4 were synthesized as the first thiophosphonate nucleosides bearing a sulfur atom at the α-position of the acyclic nucleoside phosphonates PMEA and PMPA. Thiophosphonates S-PMEA 3 and S-PMPA 4 were evaluated...

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Autores principales: Barral, Karine, Weck, Clément, Payrot, Nadine, Roux, Loic, Durafour, Céline, Zoulim, Fabien, Neyts, Johan, Balzarini, Jan, Canard, Bruno, Priet, Stéphane, Alvarez, Karine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Masson SAS. 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115536/
https://www.ncbi.nlm.nih.gov/pubmed/21803462
http://dx.doi.org/10.1016/j.ejmech.2011.06.034
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author Barral, Karine
Weck, Clément
Payrot, Nadine
Roux, Loic
Durafour, Céline
Zoulim, Fabien
Neyts, Johan
Balzarini, Jan
Canard, Bruno
Priet, Stéphane
Alvarez, Karine
author_facet Barral, Karine
Weck, Clément
Payrot, Nadine
Roux, Loic
Durafour, Céline
Zoulim, Fabien
Neyts, Johan
Balzarini, Jan
Canard, Bruno
Priet, Stéphane
Alvarez, Karine
author_sort Barral, Karine
collection PubMed
description 9-[2-(Thiophosphonomethoxy)ethyl]adenine 3 and (R)-9-[2-(Thiophosphonomethoxy)propyl]adenine 4 were synthesized as the first thiophosphonate nucleosides bearing a sulfur atom at the α-position of the acyclic nucleoside phosphonates PMEA and PMPA. Thiophosphonates S-PMEA 3 and S-PMPA 4 were evaluated for in vitro activity against HIV-1 (subtypes A to G), HIV-2 and HBV-infected cells, and found to exhibit potent antiretroviral activity. We showed that their diphosphate forms S-PMEApp 5 and S-PMPApp 6 are readily incorporated by wild-type (WT) HIV-1 RT into DNA and act as DNA chain terminators. Compounds 3 and 4 were evaluated for in vitro activity against a broad panel of DNA and RNA viruses and displayed beside HIV a moderate activity against herpes simplex virus and vaccinia viruses. In order to measure enzymatic stabilities of the target derivatives 3 and 4, kinetic data and decomposition pathways were studied at 37 °C in several media.
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spelling pubmed-71155362020-04-02 Acyclic nucleoside thiophosphonates as potent inhibitors of HIV and HBV replication Barral, Karine Weck, Clément Payrot, Nadine Roux, Loic Durafour, Céline Zoulim, Fabien Neyts, Johan Balzarini, Jan Canard, Bruno Priet, Stéphane Alvarez, Karine Eur J Med Chem Article 9-[2-(Thiophosphonomethoxy)ethyl]adenine 3 and (R)-9-[2-(Thiophosphonomethoxy)propyl]adenine 4 were synthesized as the first thiophosphonate nucleosides bearing a sulfur atom at the α-position of the acyclic nucleoside phosphonates PMEA and PMPA. Thiophosphonates S-PMEA 3 and S-PMPA 4 were evaluated for in vitro activity against HIV-1 (subtypes A to G), HIV-2 and HBV-infected cells, and found to exhibit potent antiretroviral activity. We showed that their diphosphate forms S-PMEApp 5 and S-PMPApp 6 are readily incorporated by wild-type (WT) HIV-1 RT into DNA and act as DNA chain terminators. Compounds 3 and 4 were evaluated for in vitro activity against a broad panel of DNA and RNA viruses and displayed beside HIV a moderate activity against herpes simplex virus and vaccinia viruses. In order to measure enzymatic stabilities of the target derivatives 3 and 4, kinetic data and decomposition pathways were studied at 37 °C in several media. Elsevier Masson SAS. 2011-09 2011-07-01 /pmc/articles/PMC7115536/ /pubmed/21803462 http://dx.doi.org/10.1016/j.ejmech.2011.06.034 Text en Copyright © 2011 Elsevier Masson SAS. 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
Barral, Karine
Weck, Clément
Payrot, Nadine
Roux, Loic
Durafour, Céline
Zoulim, Fabien
Neyts, Johan
Balzarini, Jan
Canard, Bruno
Priet, Stéphane
Alvarez, Karine
Acyclic nucleoside thiophosphonates as potent inhibitors of HIV and HBV replication
title Acyclic nucleoside thiophosphonates as potent inhibitors of HIV and HBV replication
title_full Acyclic nucleoside thiophosphonates as potent inhibitors of HIV and HBV replication
title_fullStr Acyclic nucleoside thiophosphonates as potent inhibitors of HIV and HBV replication
title_full_unstemmed Acyclic nucleoside thiophosphonates as potent inhibitors of HIV and HBV replication
title_short Acyclic nucleoside thiophosphonates as potent inhibitors of HIV and HBV replication
title_sort acyclic nucleoside thiophosphonates as potent inhibitors of hiv and hbv replication
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115536/
https://www.ncbi.nlm.nih.gov/pubmed/21803462
http://dx.doi.org/10.1016/j.ejmech.2011.06.034
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