Document Detail


Deglycosylation of antiherpesviral 5-substituted arabinosyluracil derivatives by rat liver extract and enterobacteria cells.
MedLine Citation:
PMID:  7702634     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A number of antiherpesviral 5-substituted derivatives of 1-beta-D-arabinofuranosyluracil (araU) were significantly resistant to phosphorolysis by rat liver extract (S-9), but were gradually deglycosylated in a 2% enterobacteria cell suspension. The relative order of the resistance conferred by the different C-5 substituents was: 5-propynyl > 5-(E)-2-bromovinyl > 5-(E)-2-chlorovinyl > 5-methyl > 5-iodo. The 2'-fluoro derivatives of araU were completely resistant to phosphorolysis by both liver extract and enterobacteria, whereas the corresponding ribofuranosyl and 2'-deoxyribofuranosyl nucleosides were easily phosphorolysed by S-9, and were immediately cleaved in a 1% enterobacteria cell suspension. These findings suggest that antiherpesviral 5-substituted araU analogues can be relatively stable in vivo, when injected intravenously, and that degradation of 1-beta-D-arabinofuranosyl-5-(E-2-bromovinyl)uracil (sorivudine) following oral administration is due primarily to the action of enterobacteria.
Authors:
H Machida; Y Watanabe; F Kano; S Sakata; M Kumagai; T Yamaguchi
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  49     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  1995 Mar 
Date Detail:
Created Date:  1995-05-02     Completed Date:  1995-05-02     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  763-6     Citation Subset:  IM    
Affiliation:
Biology Laboratory, R & D Division, Yamasa Corporation, Choshi, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antiviral Agents / metabolism*,  pharmacology
Arabinofuranosyluracil / analogs & derivatives*,  metabolism,  pharmacology
Biotransformation
Glycosylation
Herpesvirus 1, Human / drug effects
Herpesvirus 3, Human / drug effects
Klebsiella pneumoniae / metabolism*
Liver / metabolism*
Rats
Chemical
Reg. No./Substance:
0/Antiviral Agents; 3083-77-0/Arabinofuranosyluracil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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