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Evaluation of novel phosphoramidate ProTides of the 2'-fluoro derivatives of a potent anti-varicella zoster virus bicyclic nucleoside analogue
journal contribution
posted on 2023-06-08, 21:50 authored by Marco Derudas, Maurizio Quintiliani, Andrea Brancale, Graciela Andrei, Robert Snoeck, Jan Balzarini, Christopher McGuiganBackground: Recently, the synthesis and antiviral activity of a series of 2'-fluoro derivatives of the most potent anti-varicella zoster virus (VZV) agent reported to date, the bicyclic nucleoside analogue Cf1743, have been reported. Methods: Here, we present molecular modelling studies for the interaction of these compounds with VZV-encoded thymidine kinase (TK) and we report the synthesis of a series of phosphoramidate ProTides of these compounds designed to bypass the nucleoside kinase dependence of the parent nucleoside analogues. Results: The phosphoramidate prodrugs were equally effective as their parent compounds against VZV in cell culture, but lost antiviral potency against TK-deficient VZV strains. Conclusions: ProTide-based kinase bypass is not successful in this case.
History
Publication status
- Published
Journal
Antiviral Chemistry and ChemotherapyISSN
2040-2066Publisher
International Medical PressExternal DOI
Issue
1Volume
21Page range
15-31Department affiliated with
- Chemistry Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2015-07-23Usage metrics
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