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Inhibition of murine macrophage nitric oxide synthase expression by a pivoxil prodrug of antiviral acyclic nucleotide analogue 9-(2-phosphonomethoxyethyl)adenine.

Authors
  • Zídek, Z
  • Franková, D
  • Holý, A
  • Boubelík, M
  • Dráber, P
Type
Published Article
Journal
Biochemical Pharmacology
Publisher
Elsevier
Publication Date
Oct 15, 1997
Volume
54
Issue
8
Pages
855–861
Identifiers
PMID: 9354585
Source
Medline
License
Unknown

Abstract

The effect of the acyclic nucleotide analogue, 9-(2-phosphonomethoxyethyl)adenine (PMEA, Adefovir), and its (bis)pivaloyloxymethyl ester (bis-POM-PMEA, Adefovir Dipivoxil) on in vitro nitric oxide (NO) production by murine peritoneal macrophages was investigated. Bis-POM-PMEA inhibited in a concentration-dependent manner the formation of NO generated by interferon-gamma and lipopolysaccharide, the IC50 being 15 microM. Suppressed transcription of mRNA for inducible NO synthase (EC 1.14.13.39) resulting in decreased synthesis of NO synthase protein was found. Parent compound PMEA was virtually ineffective.

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