Elsevier

Biochemical Pharmacology

Volume 20, Issue 11, November 1971, Pages 3119-3123
Biochemical Pharmacology

Mechanism of inhibition of ribonucleoside diphosphate reductase by ga-(n)-heterocyclic aldehyde thiosemicarbazones

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Abstract

Methyl and benzo derivatives of 2-formylpyridine thiosemicarbazone were shown to be potent inhibitors of the ribonucleoside diphosphate reductase of the Novikoff hepatoma. Blockade of enzyme activity correlated with the ability of the various agents to retard the incorporation of 3H-thymidine into DNA of Sarcoma 180 ascites cells in vitro. Structure-activity relationships suggested that position six of 2-formylpyridine thiosemicarbazone and position three of 1-formylisoquinoline thiosemicarbazone are comparable with respect to orientation at the inhibitor binding site and that the enzyme has little bulk tolerance at this locus.

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    This work was supported by Grants CA-04464 and CA-02817 from the National Cancer Institute, United States Public Health Service, and T-23 from the American Cancer Society.

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