Synthesis of 3′-modified xylofuranosyl nucleosides bearing 5′-silyl or -butyryl groups and their antiviral effect against RNA viruses

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00619387" target="_blank" >RIV/61388963:_____/25:00619387 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1016/j.ejps.2025.107107" target="_blank" >https://doi.org/10.1016/j.ejps.2025.107107</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejps.2025.107107" target="_blank" >10.1016/j.ejps.2025.107107</a>

Result language

angličtina

Original language name

Synthesis of 3′-modified xylofuranosyl nucleosides bearing 5′-silyl or -butyryl groups and their antiviral effect against RNA viruses

Original language description

D-xylofuranosyl nucleoside analogues bearing alkylthio and glucosylthio substituents at the C3′-position were prepared by photoinitiated radical-mediated hydrothiolation reactions from the corresponding 2′,5′-di-O-silyl-3′-exomethylene uridine. Sequential desilylation and 5′-O-butyrylation of the 3′-thiosubstituted molecules produced a 24-membered nucleoside series with diverse substitution patterns, and the compounds were evaluated for their in vitro antiviral activity against three dangerous human RNA viruses, SARS-CoV-2, SINV and CHIKV. Eight compounds exhibited SARS-CoV-2 activity with low micromolar EC50 values in Vero E6 cells, and two of them also inhibited virus growth in human Calu cells. The best anti-SARS-CoV-2 activity was exhibited by 2′,5′-di-O-silylated 3′-C-alkylthio nucleosides. Twelve compounds showed in vitro antiviral activity against CHIKV and fourteen against SINV with low micromolar EC50 values, with the 5′-butyryl-2′-silyl-3′-alkylthio substitution pattern being the most favorable against both viruses. In the case of the tested nucleosides, removal of the 2′-O-silyl group completely abolished the antiviral activity of the compounds against all three viruses. Overall, the most potent antiviral agent was the disilylated 3′-glucosylthio xylonucleoside, which showed excellent and specific antiviral activity against SINV with an EC50 value of 3 μM and no toxic effect at the highest tested concentration of 120 μM.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10607 - Virology

Project

<a href="/en/project/LX22NPO5103" target="_blank" >LX22NPO5103: National Institute of Virology and Bacteriology</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

European Journal of Pharmaceutical Sciences

ISSN

0928-0987

e-ISSN

1879-0720

Volume of the periodical

209

Issue of the periodical within the volume

June

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

12

Pages from-to

107107

UT code for WoS article

001479331100001

EID of the result in the Scopus database

2-s2.0-105003303304