Abstract:
:A nonnaturally occurring L-configuration nucleoside analog, L-beta-5-bromovinyl-(2-hydroxymethyl)-1,3-(dioxolanyl)uracil (L-BVOddU) selectively inhibited varicella-zoster virus growth in human embryonic lung (HEL) 299 cell culture with an EC(50) of 0.055 microM, whereas no inhibition of CEM and HEL 299 cell growth or mitochondrial DNA synthesis was observed at concentrations up to 200 microM. L-BVOddU was phosphorylated by viral thymidine kinase but not by human cytosolic thymidine kinase, and the antiviral activity of this compound is dependent on the viral thymidine kinase. Unlike other D-configuration bromovinyl deoxyuridine analogs, such as E-5-(2-bromovinyl)-2'-deoxyuridine and 1-beta-arabinofuranosyl-E-5-(2-bromovinyl)uracil, this compound was metabolized only to its monophosphate metabolite. The di- or triphosphate metabolites were not detected. This suggested that the inhibitory mechanism may be unique and different from other anti-herpesvirus nucleoside analogs.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Li L,Dutschman GE,Gullen EA,Tsujii E,Grill SP,Choi Y,Chu CK,Cheng YCdoi
10.1124/mol.58.5.1109keywords:
subject
Has Abstractpub_date
2000-11-01 00:00:00pages
1109-14issue
5eissn
0026-895Xissn
1521-0111journal_volume
58pub_type
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