Cytotoxicity of pivoxil esters of antiviral acyclic nucleoside phosphonates: adefovir dipivoxil versus adefovir
Language English Country Czech Republic Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
16601779
DOI
10.5507/bp.2005.049
Knihovny.cz E-resources
- MeSH
- Adenine analogs & derivatives toxicity MeSH
- Antiviral Agents toxicity MeSH
- Reverse Transcriptase Inhibitors toxicity MeSH
- Cells, Cultured MeSH
- Lymphocytes drug effects MeSH
- Macrophages drug effects metabolism MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Organophosphonates toxicity MeSH
- Nitric Oxide metabolism MeSH
- Prodrugs toxicity MeSH
- Cell Proliferation drug effects MeSH
- Cell Survival drug effects MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- adefovir dipivoxil MeSH Browser
- adefovir MeSH Browser
- Adenine MeSH
- Antiviral Agents MeSH
- Reverse Transcriptase Inhibitors MeSH
- Organophosphonates MeSH
- Nitric Oxide MeSH
- Prodrugs MeSH
Biological effectiveness of antiviral acyclic nucleoside phosphonate adefo vir, 9-[2-(phosphonomethoxy)ethy]ade nine (PMEA) and its more lipophilic (bis)pivaloyloxymethyl ester prodrug adefovir dipivoxil (bis-POM-PMEA) were compared under in vitro conditions in mammalian cell systems. Proliferation of murine splenocytes was inhibited in a concentration-dependent manner, the bis-POM-PMEA being more effective than PMEA. In contrast to PMEA, bis-POM-PMEA inhibited production of nitric oxide (NO) in macrophages activated with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). Viability of both splenocytes and macrophages remained uninfluenced by PMEA, whereas pronounced cytocidal effects were exhibited by bis-POM-PMEA. The IC(50)s reached the values of 15 microM and 30 microM in cultures of macrophages and splenocytes, respectively (assayed at the interval of 24 hrs). The effects could partly be mimicked by formaldehyde, a decomposition product of the pivoxil moiety of bis-POM-PMEA. The other possible product, pivalic acid, was ineffective in this respect. The present data are consistent with the view that pivoxil prodrug of PMEA, bis-POM-PMEA possesses enhanced but also broader spectrum of biological effects than the parent compound.
References provided by Crossref.org
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