Publication Date


Document Type


First Advisor

Hagen, Timothy J.

Degree Name

M.S. (Master of Science)

Legacy Department

Department of Chemistry and Biochemistry


Enzyme inhibitors; Enzymes--Synthesis; Antibacterial agents


This thesis explores the inhibition of the IspE enzyme, found within the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway, using a variety of molecular scaffolds for the development of potential antibacterial agents. This research involved two distinct projects: First, the design of an improved synthetic route for MEP. MEP is the substrate utilized in the IspD reaction and can be converted enzymatically to produce CDP-ME, the substrate for IspE. Therefore, MEP is a valuable compound that is necessary for our IspD and IspE inhibition assays. Second, the design and synthesis of two different scaffold series was implemented for the purpose of developing IspE inhibitors. The first series contained the 2-indolinone scaffold and was screened for its antibacterial properties against 9 bacterial strains. Two compounds had large zones of inhibition at 1 mM against all tested organisms indicating moderate antibacterial activity. The second series incorporated an oxadiazole ring with either an indole or a benzothiazole ring attached. These compounds were screened against Burkholderia thailandensis and Escherichia coli IspE utilizing a thermal shift assay and an enzyme inhibition assay. The compounds were also tested against 9 bacterial strains. Three compounds had low micromolar IC50 values against E. coli IspE. There was a range of activity between the 15 compounds in this series permitting the determination of a structure-activity relationship (SAR).


Advisors: Timothy J. Hagen.||Committee members: James R. Horn; Lee S. Sunderlin.||Includes bibliographical references.||Includes illustrations.


ix, 128 pages




Northern Illinois University

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