Synthesis, antiviral evaluation, and computational studies of cyclobutane and cyclobutene L-nucleoside analogues

Rosa Miralles-Llumà, Antoni Figueras, Félix Busqué, Angel Alvarez-Larena, Jan Balzarini, Marta Figueredo, Josep Font, Ramon Alibés, Jean Didier Maréchal

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

This paper describes the stereoselective synthesis of a series of functionalized cyclobutane and cyclobutene L-nucleoside analogues featuring a methylene spacer between the carbocycle and the nucleobase. These L-nucleoside analogues were subjected to comprehensive screening for antiviral activity. To obtain knowledge at the molecular structural level relevant for designing future analogues, the mechanism of action of these L-nucleoside analogues as anti-herpes simplex virus agents was investigated by computational approaches. In particular, protein-ligand docking calculations were used to rationalize the ability of the prodrug candidates to be activated. Docking experiments were performed on the three kinases involved in the activation process of thymine and guanine derivatives. Cyclobutane and cyclobutene L-nucleoside analogues have been synthesized and screened for antiviral activity. The mechanism of action of their activation process as anti-herpes simplex virus agents has been investigated by computational approaches. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Original languageEnglish
Pages (from-to)7761-7775
JournalEuropean Journal of Organic Chemistry
Issue number34
DOIs
Publication statusPublished - 1 Dec 2013

Keywords

  • Antiviral agents
  • Carbocycles
  • Molecular modeling
  • Nucleosides

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