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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Ltd.
2011
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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. |
format | Online Article Text |
id | pubmed-7127853 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Elsevier Ltd. |
record_format | MEDLINE/PubMed |
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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