DEGLYCOSYLATION OF ANTIHERPESVIRAL 5-SUBSTITUTED ARABINOSYLURACIL DERIVATIVES BY RAT-LIVER EXTRACT AND ENTEROBACTERIA CELLS

被引：14

作者：

MACHIDA, H

WATANABE, Y

KANO, F

SAKATA, S

KUMAGAI, M

YAMAGUCHI, T

机构：

[1] YAMASA CORP,DIV RES & DEV,CHEM LAB,CHOSHI,CHIBA 288,JAPAN

[2] NISHI TOKYO UNIV,DEPT BIOL SCI,YAMANASHI 40901,JAPAN

来源：

BIOCHEMICAL PHARMACOLOGY | 1995年 / 49卷 / 06期

关键词：

ANTIHERPESVIRUS; BV-ARAU; PYRIMIDINE NUCLEOSIDE ANALOGS; DEGLYCOSYLATION; ENTEROBACTERIA; PYRIMIDINE PHOSPHORYLASE;

D O I：

10.1016/0006-2952(94)00543-U

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：763 / 766

页数：4

共 17 条

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