Synergistic activity of purine metabolism inhibitors in cultured human tumor cells.

Abstract:

:Cytotoxic effects of 3-deazaguanosine (3-DGUO) result from the inhibition of DNA synthesis and incorporation of the drug into DNA. Synergistic antiproliferative effects of a combination of 3-deazaguanosine and 2-beta-D-ribofuranosylthiazole-4-carboxamide, a potent inhibitor of inosine monophosphate dehydrogenase, was observed in human tumor cells. Inosine reversed the antiproliferative effects of the 3-deazaguanosine but not 2-beta-D-ribofuranosylthiazole-4-carboxamide. 3-Deazaguanosine monophosphate was shown to inhibit the activity of the de novo purine synthesis enzyme, 5'-phosphoribosyl-5-aminoimidazole-4-carboxamide transformylase. The data suggested a cytotoxic effect of 3-DGUO associated with the inhibition of de novo purine synthesis by drug nucleotides, an effect which may account for the synergistic action noted.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Jacobsen SJ,Page T,Diala ES,Nyhan WL,Robins RK,Mangum JH

doi

10.1016/0304-3835(87)90061-9

subject

Has Abstract

pub_date

1987-04-01 00:00:00

pages

97-104

issue

1

eissn

0304-3835

issn

1872-7980

pii

0304-3835(87)90061-9

journal_volume

35

pub_type

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