0619387 - ÚOCHB 2026 RIV NL eng J - Článek v odborném periodiku
Bege, M. - Leiner, K. - Lovas, M. - Pető, R. - Bereczki, I. - Hodek, Jan - Weber, Jan - Kuczmog, A. - Borbás, A.
Synthesis of 3′-modified xylofuranosyl nucleosides bearing 5′-silyl orbutyryl groups and their antiviral effect against RNA viruses.
European Journal of Pharmaceutical Sciences. Roč. 209, June (2025), č. článku 107107. ISSN 0928-0987. E-ISSN 1879-0720
Grant CEP: GA MŠMT(CZ) LX22NPO5103
Institucionální podpora: RVO:61388963
Klíčová slova: severe acute respiratory syndrome coronavirus (SARS-CoV-2) * chikungunya virus (CHIKV) * sindbis virus (SINV) * nucleoside analogue antivirals * photochemical thiol-ene reaction
Impakt faktor: 4.3, rok: 2023 ; AIS: 0.66, rok: 2023
Způsob publikování: Open access
Web výsledku:
https://doi.org/10.1016/j.ejps.2025.107107DOI: https://doi.org/10.1016/j.ejps.2025.107107

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.
Trvalý link: https://hdl.handle.net/11104/0366122