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Sofosbuvir Thio-analogues: Synthesis and Antiviral Evaluation of the First Novel Pyridine- and Pyrimidine-Based Thioglycoside Phosphoramidates

[Image: see text] The synthesis and antiviral screening of the first reported series of pyridine- and pyrimidine-based thioglycoside phosphoramidates are herein reported. They were prepared through two synthetic steps: The first step is via coupling of mercapto-derivatized heterocyclic bases with th...

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Autores principales: Abu-Zaied, Mamdouh Attia, Hammad, Sherif F., Halaweish, Fathi T., Elgemeie, Galal Hamza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315579/
https://www.ncbi.nlm.nih.gov/pubmed/32596602
http://dx.doi.org/10.1021/acsomega.0c01364
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author Abu-Zaied, Mamdouh Attia
Hammad, Sherif F.
Halaweish, Fathi T.
Elgemeie, Galal Hamza
author_facet Abu-Zaied, Mamdouh Attia
Hammad, Sherif F.
Halaweish, Fathi T.
Elgemeie, Galal Hamza
author_sort Abu-Zaied, Mamdouh Attia
collection PubMed
description [Image: see text] The synthesis and antiviral screening of the first reported series of pyridine- and pyrimidine-based thioglycoside phosphoramidates are herein reported. They were prepared through two synthetic steps: The first step is via coupling of mercapto-derivatized heterocyclic bases with the appropriate α-bromo per-acetylated sugars. The second one is the hydrolysis of the acetate esters under basic conditions that were consequently conjugated with the phosphoramidating reagent to afford the desired thioglycoside protides. Eight compounds were evaluated for their antiviral activities against different viral cell lines, namely, adenovirus 7, HAV (hepatitis A) HM175, Coxsackievirus B4, and HSV-1 (herpes simplex virus type 1), in addition to the antiviral bioassay against ED-43/SG-Feo (VYG) replicon of HCV (hepatitis C virus) genotype 4a. Both compounds 5b and 11 showed notable antiviral activity against Coxsackie virus B4, reflected from the CC(50) values of 17 and 20 μg/100 μL and IC(50) values of 4.5 and 6.0 μg/100 μL, respectively. Same two compounds elicited remarkable activities toward herpes simplex virus type 1, represented by CC(50) values of 17 and 16 μg/100 μL and IC(50) values of 6.3 and 6.6 μg/100 μL, respectively. Combination of 11 with acyclovir elicited a notable synergistic activity in comparison with acyclovir alone, as inferred from herpes simplex polymerase enzyme inhibitory assay values of 2.64 and 4.78 μg/100 mL, respectively. Only compound 11 elicited a remarkable activity against HCV. Potential promising activities of compound 11 have been shown with respect to CC(50), IC(50), and enzyme assay inhibitory activities.
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spelling pubmed-73155792020-06-26 Sofosbuvir Thio-analogues: Synthesis and Antiviral Evaluation of the First Novel Pyridine- and Pyrimidine-Based Thioglycoside Phosphoramidates Abu-Zaied, Mamdouh Attia Hammad, Sherif F. Halaweish, Fathi T. Elgemeie, Galal Hamza ACS Omega [Image: see text] The synthesis and antiviral screening of the first reported series of pyridine- and pyrimidine-based thioglycoside phosphoramidates are herein reported. They were prepared through two synthetic steps: The first step is via coupling of mercapto-derivatized heterocyclic bases with the appropriate α-bromo per-acetylated sugars. The second one is the hydrolysis of the acetate esters under basic conditions that were consequently conjugated with the phosphoramidating reagent to afford the desired thioglycoside protides. Eight compounds were evaluated for their antiviral activities against different viral cell lines, namely, adenovirus 7, HAV (hepatitis A) HM175, Coxsackievirus B4, and HSV-1 (herpes simplex virus type 1), in addition to the antiviral bioassay against ED-43/SG-Feo (VYG) replicon of HCV (hepatitis C virus) genotype 4a. Both compounds 5b and 11 showed notable antiviral activity against Coxsackie virus B4, reflected from the CC(50) values of 17 and 20 μg/100 μL and IC(50) values of 4.5 and 6.0 μg/100 μL, respectively. Same two compounds elicited remarkable activities toward herpes simplex virus type 1, represented by CC(50) values of 17 and 16 μg/100 μL and IC(50) values of 6.3 and 6.6 μg/100 μL, respectively. Combination of 11 with acyclovir elicited a notable synergistic activity in comparison with acyclovir alone, as inferred from herpes simplex polymerase enzyme inhibitory assay values of 2.64 and 4.78 μg/100 mL, respectively. Only compound 11 elicited a remarkable activity against HCV. Potential promising activities of compound 11 have been shown with respect to CC(50), IC(50), and enzyme assay inhibitory activities. American Chemical Society 2020-06-09 /pmc/articles/PMC7315579/ /pubmed/32596602 http://dx.doi.org/10.1021/acsomega.0c01364 Text en Copyright © 2020 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Abu-Zaied, Mamdouh Attia
Hammad, Sherif F.
Halaweish, Fathi T.
Elgemeie, Galal Hamza
Sofosbuvir Thio-analogues: Synthesis and Antiviral Evaluation of the First Novel Pyridine- and Pyrimidine-Based Thioglycoside Phosphoramidates
title Sofosbuvir Thio-analogues: Synthesis and Antiviral Evaluation of the First Novel Pyridine- and Pyrimidine-Based Thioglycoside Phosphoramidates
title_full Sofosbuvir Thio-analogues: Synthesis and Antiviral Evaluation of the First Novel Pyridine- and Pyrimidine-Based Thioglycoside Phosphoramidates
title_fullStr Sofosbuvir Thio-analogues: Synthesis and Antiviral Evaluation of the First Novel Pyridine- and Pyrimidine-Based Thioglycoside Phosphoramidates
title_full_unstemmed Sofosbuvir Thio-analogues: Synthesis and Antiviral Evaluation of the First Novel Pyridine- and Pyrimidine-Based Thioglycoside Phosphoramidates
title_short Sofosbuvir Thio-analogues: Synthesis and Antiviral Evaluation of the First Novel Pyridine- and Pyrimidine-Based Thioglycoside Phosphoramidates
title_sort sofosbuvir thio-analogues: synthesis and antiviral evaluation of the first novel pyridine- and pyrimidine-based thioglycoside phosphoramidates
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315579/
https://www.ncbi.nlm.nih.gov/pubmed/32596602
http://dx.doi.org/10.1021/acsomega.0c01364
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