Your browser doesn't support javascript.
Extension of furopyrimidine nucleosides with 5-alkynyl substituent: Synthesis, high fluorescence, and antiviral effect in the absence of free ribose hydroxyl groups.
Kaczmarek, Renata; Twardy, Dylan J; Olson, Trevor L; Korczynski, Dariusz; Andrei, Graciela; Snoeck, Robert; Dolot, Rafal; Wheeler, Kraig A; Dembinski, Roman.
  • Kaczmarek R; Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363, Lódz, Poland.
  • Twardy DJ; Department of Chemistry, Oakland University, 146 Library Drive, Rochester, MI, 48309-4479, USA.
  • Olson TL; Department of Chemistry, Oakland University, 146 Library Drive, Rochester, MI, 48309-4479, USA.
  • Korczynski D; Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363, Lódz, Poland.
  • Andrei G; Rega Institute, Department of Microbiology, Immunology and Transplantation, Herestraat 49, 3000, Leuven, Belgium.
  • Snoeck R; Rega Institute, Department of Microbiology, Immunology and Transplantation, Herestraat 49, 3000, Leuven, Belgium.
  • Dolot R; Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363, Lódz, Poland.
  • Wheeler KA; Department of Chemistry, Whitworth University, 300 W. Hawthorne Rd., Spokane, WA, 99251, USA.
  • Dembinski R; Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363, Lódz, Poland; Department of Chemistry, Oakland University, 146 Library Drive, Rochester, MI, 48309-4479, USA. Electronic address: dembinsk@oakland.edu.
Eur J Med Chem ; 209: 112884, 2021 Jan 01.
Article in English | MEDLINE | ID: covidwho-800277
Semantic information from SemMedBD (by NLM)
1. Nucleosides compared_with Nucleosides
Subject
Nucleosides
Predicate
compared_with
Object
Nucleosides
2. Nucleosides compared_with Nucleosides
Subject
Nucleosides
Predicate
compared_with
Object
Nucleosides
ABSTRACT
A novel methodology to access alkynyl nucleoside analogues is elaborated. Highly fluorescent 5-alkynylfuropyrimidines were synthesized (97-46%) and their antiviral properties investigated in vitro. Regiochemistry of the functionalization was achieved with the aid of 5-endo-dig electrophilic halocyclization of acetyl 5-p-tolyl- or 5-p-pentylphenyl-2'-deoxyuridine. Structure of one of the resulting nucleosides, 6-p-tolyl-5-iodo-2'-deoxyribofuranosyl-furo[2,3-d]pyrimidin-2-one, was confirmed by X-ray crystallography, and its conformation was compared to related nucleosides. Diverse alkynyl substituents were introduced at the heterobicyclic base C-5 position via Sonogashira coupling of 5-iodo-2'-deoxyribofuranosyl-furo[2,3-d]pyrimidin-2-ones. The resulting compounds had fluorescence emissions of 452-481 nm. High quantum yields of 0.53-0.60 were observed for 9-ethynyl-9-fluorenol and propargyl alcohol/methyl ether-modified furopyrimidines. These modified nucleosides, designed in the form of ribose acetyl esters, are potential tools for fluorescent tagging, studying nucleoside metabolism, 2'-deoxyribonucleoside kinase activity, and antiviral activity. Antiviral assays against a broad spectrum of DNA and RNA viruses showed that in human embryonic lung (HEL) cell cultures some of the compounds posess antiviral activity (EC50 1.3-13.2 µM) against varicella-zoster virus (VZV). The alkynyl furopyrimidine with two p-pentylphenyl substituents emerged as the best compound with reasonable and selective anti-VZV activity, confirming p-pentylphenyl potency as a pharmacophore.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Pyrimidine Nucleosides Type of study: Experimental Studies / Randomized controlled trials Limits: Humans Language: English Journal: Eur J Med Chem Year: 2021 Document Type: Article Affiliation country: J.ejmech.2020.112884

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Pyrimidine Nucleosides Type of study: Experimental Studies / Randomized controlled trials Limits: Humans Language: English Journal: Eur J Med Chem Year: 2021 Document Type: Article Affiliation country: J.ejmech.2020.112884