Graduation Semester and Year

2016

Language

English

Document Type

Thesis

Degree Name

Master of Science in Chemistry

Department

Chemistry and Biochemistry

First Advisor

Frank W Foss

Abstract

Antibiotics play a vital role in fighting infectious disease caused by bacterial species. Antimicrobial resistance has been shown for every current antibiotic and poses a major health risk. To combat these growing threats to human health; new molecules must be investigated to treat bacterial infection. Chemical inhibition of the vitamin B1 biosynthetic pathway in the bacterial cell was hypothesized to inhibit the survival of bacteria. A series of synthetic molecules, which resemble metabolites of the vitamin B1 pathway, exhibit the inhibition of specific enzymes within this pathway and display initial activity against bacterial growth and survival. The beneficial activity of these new molecules was interpreted both experimentally and computationally. By investigating the relationship between molecular structure and biological function, a second generation of molecules was designed and a number of them were synthesized to be more potent inhibitors of bacterial growth. This iterative process - involving structural design, chemical synthesis and biological evaluation - reveals the vitamin B1 biosynthetic pathway to be a potential new avenue for antibiotic development to treat human infection.

Keywords

Antibiotics, Inhibition, Drug design

Disciplines

Chemistry | Physical Sciences and Mathematics

Comments

Degree granted by The University of Texas at Arlington

Included in

Chemistry Commons

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