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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10607 - Virology

Projekt

<a href="/cs/project/LX22NPO5103" target="_blank" >LX22NPO5103: Národní institut virologie a bakteriologie</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

European Journal of Pharmaceutical Sciences

ISSN

0928-0987

e-ISSN

1879-0720

Svazek periodika

209

Číslo periodika v rámci svazku

June

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

12

Strana od-do

107107

Kód UT WoS článku

001479331100001

EID výsledku v databázi Scopus

2-s2.0-105003303304