Inhibitor properties of some 5-substituted uracil acyclonucleosides, and 2,2'-anhydrouridines versus uridine phosphorylase from E. coli and mammalian sources

Alicja K. Drabikowska, Lidia Lissowska, Z. Veres, David Shugar

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Abstract

Two series of 5-substituted uracil N(1)-acyclonucleosides, each with a different acyclic chain, were examined as inhibitors of uridine phosphorylase from rat intestinal mucosa, and several against the enzyme from Ehrlich ascites cells. In addition, several 5-substituted analogues of 2,2'-anhydrouridine were tested for their inhibitory effects vs a highly purified uridine phosphorylase fromEscherichia coli. The results are compared with previously published data for inhibition of the E. coli enzyme by the acyclonucleosides, and of the rat enzyme by the anhydrouridines. In all instances, the inhibitors were active only vs the uridine, but not thymidine, phosphorylase from E. coli, and inhibition was competitive with respect to uridine as substrate. In general, with one or two exceptions, inhibitory effects were more pronounced against the enzyme from mammalian sources. Amongst the acyclonucleoside analogues, the most effective inhibitor of the enzyme from the rat and Ehrlich ascites cells exhibited a Ki = 0.1 μM, comparable to that reported with the Sarcoma-180 enzyme, whereas the Ki for inhibition of theE. coli enzyme was 0.7μM. By contrast, another effective inhibitor of the bacterial enzyme was 7-fold less potent against the mammalian enzyme. The 2,2'-anhydrouridines were 10- to 30-fold more effective against the rat, as compared to the E. coli, enzyme. The overall quantitative data provide a reasonably good basis for the further design of potent inhibitors for possible use in chemotherapy.

Original languageEnglish
Pages (from-to)4125-4128
Number of pages4
JournalBiochemical Pharmacology
Volume36
Issue number23
DOIs
Publication statusPublished - Dec 1 1987

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Uridine Phosphorylase
Uracil
Escherichia coli
Enzymes
Rats
Uridine
Enzyme Inhibitors
Ascites
Thymidine Phosphorylase
Sarcoma 180
Chemotherapy
Intestinal Mucosa

ASJC Scopus subject areas

  • Pharmacology

Cite this

Inhibitor properties of some 5-substituted uracil acyclonucleosides, and 2,2'-anhydrouridines versus uridine phosphorylase from E. coli and mammalian sources. / Drabikowska, Alicja K.; Lissowska, Lidia; Veres, Z.; Shugar, David.

In: Biochemical Pharmacology, Vol. 36, No. 23, 01.12.1987, p. 4125-4128.

Research output: Contribution to journalArticle

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