Antiviral activity of cyclosaligenyl prodrugs of the nucleoside analogue bromovinyldeoxyuridine against herpes viruses

Autor: Astrid Meerbach, Andreas Sauerbrei, Heide-Marie Meckel, Chris Meier, Peter Wutzler
Rok vydání: 2006
Předmět:
Zdroj: International Journal of Antimicrobial Agents. 27:423-430
ISSN: 0924-8579
DOI: 10.1016/j.ijantimicag.2005.11.021
Popis: A series of 42 lipophilic bromovinyldeoxyuridine monophosphates (BVDUMPs) are presented as potential prodrugs of the antiviral agent (E)-5-(2-bromovinyl)-2′-deoxyuridine (BVDU). The 5′- cyclo Sal-masking group technique has been applied to this cyclic nucleoside analogue to achieve delivery of the monophosphate of BVDU inside the target cells. The new substances have been tested for their antiviral activity against herpes simplex virus types 1 and 2 (HSV-1 and -2), thymidine kinase-deficient (TK − ) HSV-1, varicella-zoster virus (VZV), human cytomegalovirus (HCMV) and Epstein–Barr virus (EBV). The XTT-based tetrazolium reduction assay EZ4U (for HSV), the plaque inhibition test (for VZV and HCMV) and a DNA hybridisation assay (for EBV) were used to assess antiviral activity. The results indicate that cyclo Sal-BVDUMP triesters proved to be potent and selective inhibitors of HSV-1 comparable with aciclovir. VZV replication was inhibited by very low concentrations, and two substances had a slightly better anti-VZV activity than the parent compound BVDU. No antiviral effect could be demonstrated against TK − -HSV-1, HSV-2 and HCMV, most likely owing to the lack of phosphorylation to BVDU diphosphate. Most remarkably, several cyclo Sal-BVDUMP triesters yielded promising anti-EBV activity whereas the parent compound BVDU was entirely inactive.
Databáze: OpenAIRE
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