Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Design, synthesis and biological evaluation of novel acyclovir ProTides

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

Full text not available from this repository.

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: Medicine
Pharmacy
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

Actions (repository staff only)

Edit Item Edit Item