Synthesis, antiviral evaluation, and computational studies of cyclobutane and cyclobutene L-nucleoside analogues
Miralles Llumà, Rosa (Universitat Autònoma de Barcelona. Departament de Química)
Figueras, Antoni (Universitat Autònoma de Barcelona. Departament de Química)
Busqué Sánchez, Félix (Universitat Autònoma de Barcelona. Departament de Química)
Alvarez-Larena, Angel (Universitat Autònoma de Barcelona. Servei de Difracció de Raigs X)
Balzarini, Jan (KU Leuven. Rega Institute for Medical Research)
Figueredo Galimany, Marta (Universitat Autònoma de Barcelona. Departament de Química)
Font i Cierco, Josep (Universitat Autònoma de Barcelona. Departament de Química)
Alibes, Ramón (Universitat Autònoma de Barcelona. Departament de Química)
Maréchal, Jean-Didier (Universitat Autònoma de Barcelona. Departament de Química)

Date:	2013
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.
Grants:	Ministerio de Economía y Competitividad CTQ2010-15380/BQU Ministerio de Ciencia e Innovación CTQ2008-06866-C02-01 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-68
Rights:	Tots els drets reservats.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	Antiviral agents ; Carbocycles ; Molecular modeling ; Nucleosides
Published in:	European journal of organic chemistry, Vol. 2013, issue 34 (Dec. 2013) , p. 7761-7775, ISSN 1099-0690

DOI: 10.1002/ejoc.201301097

Postprint 16 p, 1.1 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Experimental sciences > Synthesis of Bioactive Organic Compounds and Functional Materials (SynOrgFUN)
Articles > Research articles
Articles > Published articles