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Inhibition of ribonucleotide reductase and L1210 cell growth by N-hydroxy-N'-aminoguanidine derivatives.

Abstract：

:A series of N-hydroxy-N'-aminoguanidine derivatives was studied for their effects on L1210 cell growth and ribonucleotide reductase activity. With the twelve compounds studied, there was a good correlation between the inhibition of L1210 cell growth and the inhibition of ribonucleotide reductase activity. The most potent compound required concentrations of only 1.4 and 2 microM for 50% inhibition of L1210 cell growth and ribonucleotide reductase activity respectively. These guanidine analogs specifically inhibited the conversion of [14C]cytidine and deoxycytidine nucleotides in the nucleotide pool and the incorporation of [14C]cytidine into DNA without altering the incorporation of [14C]cytidine into RNA. Ribonucleotide reductase activity in drug-treated cells was reduced markedly. Iron-chelating agents did not either increase or decrease the inhibition caused by the N-hydroxy-N'-aminoguanidine derivatives. No evidence was obtained that these derivatives selectively inactivated one of the subunits of ribonucleotide reductase. These compounds appear to inhibit ribonucleotide reductase by a mechanism different from hydroxyurea or the thiosemicarbazone derivatives.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Cory JG,Carter GL,Bacon PE,T'ang A,Lien EJ

doi

10.1016/0006-2952(85)90561-1

subject

Has Abstract

pub_date

1985-08-01 00:00:00

pages

2645-50

issue

15

eissn

0006-2952

issn

1873-2968

pii

0006-2952(85)90561-1

journal_volume

34

pub_type

杂志文章

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