McGuigan, Christopher  ORCID: https://orcid.org/0000-0001-8409-710X, Hinsinger, Karen, Farleigh, Laura, Pathirana, Ranjith and Bugert, Joachim J. ORCID: https://orcid.org/0000-0002-0556-3211
2013.
Novel antiviral activity of l-dideoxy bicyclic nucleoside analogues versus vaccinia and measles viruses in vitro.
Journal of Medicinal Chemistry
56
(3)
, pp. 1311-1322.
10.1021/jm301778x
|
Abstract
Dideoxy bicyclic pyrimidine nucleoside analogues (ddBCNAs) with d-chirality have previously been described by us to inhibit replication of human cytomegalovirus. We herein report for the first time that activity against vaccinia virus (VACV) was achieved using novel l-analogues. A structure–activity relationship was established: Antiviral activity versus VACV was highest with an ether side chain with an optimum of n-C9H18–O–n-C5H11. This gave an IC50 of 190 nM, a 60-fold enhancement over the FDA-approved antiviral cidofovir. Interestingly, l-ddBCNAs also inhibit wild type measles virus syncytia formation with a TCID50 of 7.5 μM for the lead compound. We propose that l-ddBCNAs represent significant innovative antiviral candidates versus measles and poxviruses, and we suggest a mechanism of action versus one or more cellular targets that are essential for viral replication.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Medicine Schools > Pharmacy Research Institutes & Centres > Systems Immunity Research Institute (SIURI) |
| Subjects: | Q Science > QR Microbiology > QR180 Immunology R Medicine > RM Therapeutics. Pharmacology |
| Publisher: | American Chemical Society |
| ISSN: | 0022-2623 |
| Last Modified: | 09 Aug 2024 13:51 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/43409 |
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