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New prodrugs of Adefovir and Cidofovir

New Adefovir (PMEA) prodrugs with a pro-moiety consisting of decyl or decyloxyethyl chain bearing hydroxyl function(s), hexaethyleneglycol or a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl unit were prepared starting from the tetrabutylammonium salt of the phosphonate drug and an appropriate alkyl bromi...

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Autores principales: Tichý, Tomáš, Andrei, Graciela, Dračínský, Martin, Holý, Antonín, Balzarini, Jan, Snoeck, Robert, Krečmerová, Marcela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127853/
https://www.ncbi.nlm.nih.gov/pubmed/21565516
http://dx.doi.org/10.1016/j.bmc.2011.04.016
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author Tichý, Tomáš
Andrei, Graciela
Dračínský, Martin
Holý, Antonín
Balzarini, Jan
Snoeck, Robert
Krečmerová, Marcela
author_facet Tichý, Tomáš
Andrei, Graciela
Dračínský, Martin
Holý, Antonín
Balzarini, Jan
Snoeck, Robert
Krečmerová, Marcela
author_sort Tichý, Tomáš
collection PubMed
description New Adefovir (PMEA) prodrugs with a pro-moiety consisting of decyl or decyloxyethyl chain bearing hydroxyl function(s), hexaethyleneglycol or a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl unit were prepared starting from the tetrabutylammonium salt of the phosphonate drug and an appropriate alkyl bromide or tosylate. Analogously, two esters of Cidofovir [(S)-HPMPC] bearing a hexaethyleneglycol moiety were prepared. The activity of the prodrugs was evaluated in vitro against different virus families. A loss in the antiviral activities of the hydroxylated decyl or decyloxyethyl esters and hexaethyleneglycol esters of PMEA against human immunodeficiency virus (HIV) and herpesviruses [including herpes simplex virus (HSV), varicella-zoster virus (VZV), and human cytomegalovirus (CMV)] occurred in comparison with the parent compound. On the other hand, the (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl ester of PMEA showed significant activities against HIV and herpesviruses. (S)-HPMPC prodrugs exhibited anti-cytomegalovirus activities in the same range as the parent drug, whereas the anti-HSV and anti-VZV activities were one- to seven-fold lower than that of Cidofovir.
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spelling pubmed-71278532020-04-08 New prodrugs of Adefovir and Cidofovir Tichý, Tomáš Andrei, Graciela Dračínský, Martin Holý, Antonín Balzarini, Jan Snoeck, Robert Krečmerová, Marcela Bioorg Med Chem Article New Adefovir (PMEA) prodrugs with a pro-moiety consisting of decyl or decyloxyethyl chain bearing hydroxyl function(s), hexaethyleneglycol or a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl unit were prepared starting from the tetrabutylammonium salt of the phosphonate drug and an appropriate alkyl bromide or tosylate. Analogously, two esters of Cidofovir [(S)-HPMPC] bearing a hexaethyleneglycol moiety were prepared. The activity of the prodrugs was evaluated in vitro against different virus families. A loss in the antiviral activities of the hydroxylated decyl or decyloxyethyl esters and hexaethyleneglycol esters of PMEA against human immunodeficiency virus (HIV) and herpesviruses [including herpes simplex virus (HSV), varicella-zoster virus (VZV), and human cytomegalovirus (CMV)] occurred in comparison with the parent compound. On the other hand, the (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl ester of PMEA showed significant activities against HIV and herpesviruses. (S)-HPMPC prodrugs exhibited anti-cytomegalovirus activities in the same range as the parent drug, whereas the anti-HSV and anti-VZV activities were one- to seven-fold lower than that of Cidofovir. Elsevier Ltd. 2011-06-01 2011-04-22 /pmc/articles/PMC7127853/ /pubmed/21565516 http://dx.doi.org/10.1016/j.bmc.2011.04.016 Text en Copyright © 2011 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
Tichý, Tomáš
Andrei, Graciela
Dračínský, Martin
Holý, Antonín
Balzarini, Jan
Snoeck, Robert
Krečmerová, Marcela
New prodrugs of Adefovir and Cidofovir
title New prodrugs of Adefovir and Cidofovir
title_full New prodrugs of Adefovir and Cidofovir
title_fullStr New prodrugs of Adefovir and Cidofovir
title_full_unstemmed New prodrugs of Adefovir and Cidofovir
title_short New prodrugs of Adefovir and Cidofovir
title_sort new prodrugs of adefovir and cidofovir
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127853/
https://www.ncbi.nlm.nih.gov/pubmed/21565516
http://dx.doi.org/10.1016/j.bmc.2011.04.016
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