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

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. T...

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Detalhes bibliográficos
Autores: Miralles, Rosa|||0000-0003-4757-9593, Figueras, Antoni, Busqué, Félix|||0000-0001-7566-4264, Álvarez-Fernández, Alejandra|||0000-0002-1906-0180, Balzarini, Jan, Figueredo Galimany, Marta|||0000-0002-8278-7534, Font, Josep|||0000-0002-1244-9564, Alibés, Ramon|||0000-0002-7997-2691, Maréchal, Jean-Didier|||0000-0002-8344-9043
Formato: artículo
Fecha de publicación:2013
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:279315
Acesso em linha:https://ddd.uab.cat/record/279315
https://dx.doi.org/urn:doi:10.1002/ejoc.201301097
Access Level:acceso abierto
Palavra-chave:Antiviral agents
Carbocycles
Molecular modeling
Nucleosides
Descrição
Resumo: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.