Počet záznamů: 1
Synthesis of 3′-modified xylofuranosyl nucleosides bearing 5′-silyl orbutyryl groups and their antiviral effect against RNA viruses
- 1.
SYSNO ASEP 0619387 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve SCOPUS Název Synthesis of 3′-modified xylofuranosyl nucleosides bearing 5′-silyl orbutyryl groups and their antiviral effect against RNA viruses Tvůrce(i) Bege, M. (HU)
Leiner, K. (HU)
Lovas, M. (HU)
Pető, R. (HU)
Bereczki, I. (HU)
Hodek, Jan (UOCHB-X) RID, ORCID
Weber, Jan (UOCHB-X) RID, ORCID
Kuczmog, A. (HU)
Borbás, A. (HU)Číslo článku 107107 Zdroj.dok. European Journal of Pharmaceutical Sciences. - : Elsevier - ISSN 0928-0987
Roč. 209, June (2025)Poč.str. 12 s. Jazyk dok. eng - angličtina Země vyd. NL - Nizozemsko Klíč. slova severe acute respiratory syndrome coronavirus (SARS-CoV-2) ; chikungunya virus (CHIKV) ; sindbis virus (SINV) ; nucleoside analogue antivirals ; photochemical thiol-ene reaction CEP LX22NPO5103 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora UOCHB-X - RVO:61388963 EID SCOPUS 105003303304 DOI https://doi.org/10.1016/j.ejps.2025.107107 Anotace 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. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Rok sběru 2026 Elektronická adresa https://doi.org/10.1016/j.ejps.2025.107107
Počet záznamů: 1