The central nature of nicotinamide in metabolic processes as a part of the NAD and NADP coenzyme systems prompted the synthesis of a series of N-nicotinyl- and N-isonicotinyl-N'- (substituted)ureas as potential metabolite antagonists of the vitamin. The compounds which were synthesized may be represented by the following general structure, where R = hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, n-hexyl, cyclohexyl, phenyl and a-naphthyl. The observed toxicity of the N-nicotinyl-N'-(substituted)urea analogs may be attributed to the formation of a non-functional N-nicotinyl-N'-(substituted)urea-NAD analog through an exchange reaction catalyzed by NAD-ases in the cell. Support for this view was obtained by an in vitro enzymic synthesis of Nnicotinyl- N'-ethylurea-NAD analog employing N-nicotinyl-7- 1 4CN'- ethylurea. The labeled derivative was characterized through spectral, chromatographic, and chemical reaction studies.

5478Y7T.pdf / "In this thesis is reported the effect of propargylglycine on mammals. It was found to inhibit the growth of young white rats, and its toxicity was unexpectedly high. Most probably the toxicity is not alone due to its action as an amino acid antagonist. The minimum lethal dose was determined in young rats and adult mice. Several attempts were made to protect the experimental animals by simultaneous administration of dietary or metabolic factors. Also several possible mechanisms of action are suggested and discussed"--Introduction. / Typescript. / "January, 1953." / Submitted to the Graduate Council of Florida State University in partial fulfillment of the requirements for the degree of Master of Science. / Advisor: Karl Dittmer, Professor Directing Thesis. / Includes bibliographical references.

In these studies several different types of antimetabolites were synthesized, and their biological effects were examined in various assay systems. More extensive investigations were done in microbial systems in which many of the compounds proved to be inhibitory to growth, and attempts were made to determine the mode of biochemical action by adding supplements of the appropriate natural metabolite.

Thesis (M.Sc. (Pharmacology))--University of Pretoria, 2008. / Summary in English. Includes bibliographical references.

Thesis (M.S.)--University of Wisconsin--Madison, 1971. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1958. / Typescript. Abstracted in Dissertation abstracts, v. 19 (1958) no. 5, p. 949. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 128-133).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1956. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 53-56).

Because of the varied opinions and findings concerning the effect of cellular antimetabolites on the replication of both RNA and DNA-containing animal viruses, this project was undertaken to observe the effects of antimetabolites on Newcastle disease and vaccinia viruses: an RNA and a DNA virus respectively. The compounds chosen were the pyrimidine analogues 5-fltrorouracil and 5-iodo-deoxyuridine, and thioguanine, a purine antimetabolite. These compounds were chosen because they have already been shown to have growth inhibiting properties in other systems. Inhibition of virus replication was attempted rather than protection of cells, although some effort was made at the outset to determine the tolerance of the 10 - 12 day old chick embryo for the antimetabolites used in this study. The tolerance of the 10 - 12 day old chick was determined by inoculating the yolk sac of the developing embryo with the analogues and noting the survival time. The maximal concentration of the analogue which allowed 3 out of 4 embryos to survive for 48 hours at 37°c was the dose employed in the tests. Inoculation of the embryos with the virus was via the allantoic cavity or the chorio-allantoic membrane. Administration of the antimetabolite was made via the yolk sac either immediately after virus inoculation or if- hours later. After incubation for 36 - 48 hours at 37°C, the allantoic fluid and homogenized chorio-allantoic membranes were assayed to determine whether, there was any decrease in the production of virus-specific material in the presence of the antimetabolites. Tissue cultures of chick fibroblast cells infected with vaccinia virus were treated with antimetabolite and observed for noticeable changes. Nucleic acid analogues appear to vary in their inhibitory effects on different viruses. The enzymatic mechanism of the inhibitions seems to differ in different organisms. Antimetabolites may inhibit replication of DNA viruses and not of RNA viruses, or they may vary in degree and manner of inhibition among the DNA or RNA containing viruses themselves. 5-Fluorouracil was found to inhibit partially the replication of vaccinia virus in the chick embryo. The antimetabolite appeared to have no significant effect on the replication of Newcastle Disease virus. There were no observable differences in the titers of either virus harvested from thioguanine treated embryos as compared with-untreated embryos. / Science, Faculty of / Microbiology and Immunology, Department of / Graduate

No description available.

Proefschrift--Utrecht. / Vita. Summary in English. Includes bibliography.