Derudas, Marco, McGuigan, Christopher  ORCID: https://orcid.org/0000-0001-8409-710X, Brancale, Andrea ORCID: https://orcid.org/0000-0002-9728-3419, Bugert, Joachim Jakob ORCID: https://orcid.org/0000-0002-0556-3211, Andrei, G., Snoeck, R. and Balzarini, J.
2008.
Design, synthesis and biological evaluation of novel acyclovir ProTides.
Antiviral Research
78
(2)
, A55-A56.
10.1016/j.antiviral.2008.01.116
|
Abstract
Acyclovir and its prodrug valacyclovir are currently the treatments of choice for herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. Intracellular conversion of acyclovir to its active triphosphate form is severely limited by the first phosphorylation step, which is carried out by a herpes virus encoded thymidine kinase (Elion et al., 1977). Further conversions to the di- and triphosphate are mediated by cellular guanosine monophosphate kinase and nucleoside diphosphate kinase respectively. Importantly, the activation of the compound by the viral nucleoside kinase is a target for drug resistance in both HSV and VZV strains (Larder et al., 1983). Our phosphoramidate ProTide approach was applied to acyclovir as a means to bypass the limiting step of its activation. However, no significant improvement in antiviral activity was observed (McGuigan et al., 2000). In the present work, a new series of optimised acyclovir ProTides with an enhanced biological profile is reported (Fig. 1).
| Item Type: | Article |
|---|---|
| Status: | Published |
| Schools: | Schools > Medicine Schools > Pharmacy Research Institutes & Centres > Systems Immunity Research Institute (SIURI) |
| Publisher: | Elsevier |
| ISSN: | 0166-3542 |
| Last Modified: | 05 Jan 2024 05:55 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/6491 |
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