Date of Award

Fall 1979

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry & Biochemistry

Program/Concentration

Chemistry

Committee Director

Roy L. Williams

Committee Director

Lloyd Wolfinbarger

Committee Member

Robert L. Ake

Committee Member

R. O. Carter

Committee Member

James H. Yuan

Call Number for Print

Special Collections LD4331.C45P65

Abstract

A number of' a-(N)-heterocyclic thiosemicarbazones have been synthesized and evaluated for potential antineoplastic activity since Brockman and colleagues2 reported the antineoplastic activity of' 2-f'ormylpyridine thiosemicarbazone (1). The primary objective of' this research project has been the synthesis and characterization of' the semicarbazone and the thiosemicarbazone derivatives of' the di-2-pyridyl ketone, (9-a) and (9-b), and the 1,8-diazaf'luorenone, (10-a) and (10-b), ring systems, as well as the evaluation of' these compounds for both in vitro and in vivo antineoplastic activity against Ehrlich ascites tumor cells in mice. These studies have suggested that di-2-pyridyl ketone thiosemicarbazone (9-b) is as effective as 2-formylpyridine thiosemicarbazone (1), a known antineoplastic agent, 2 at inhibiting tumor growth in the systems used.

The generally accepted mechanism of' action suggests that the a-(N)-heterocyclic thiosemicarbazones block DNA synthesis in tumor cells by inhibiting ribonucleotide reductase, either by chelation of' the compound with the enzyme dependent ferrous ion or through a preformed metal chelate which inhibits reductase activity. Both the copper (14) and the iron (15) complexes of' di-2-pyridyl ketone thiosemicarbazone (9-b) show greater activity in vivo than the parent ligand. This would suggest that the preformed chelate is perhaps the active form of di-2-pyridyl ketone thiosemicarbazone.

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DOI

10.25777/fn08-4749

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