Design and synthesis of cyanuric acid based siderophores.

摘要

Siderophores are low molecular weight iron chelators that are used by several microorganisms to bind and transport iron through the cellular membrane. These interesting molecules can provide a new method to treat multi-drug resistant strains of pathogenic microbes.; The synthesis of a mimic of the natural siderophore rhodoturulic acid will be described in Chapter 2. The synthesis of this siderophore in large quantities enables the synthesis of several siderophore-drug conjugates that can be utilized against multiple targets.; It is uncertain whether fungi utilize siderophores in order to acquire iron, therefore, several antifungal siderophore conjugates were synthesized and tested as described in Chapter 3. The study of these conjugates provided a broader understanding of the activity and viability of siderophore-drug conjugates against fungi.; Fluorescent siderophore conjugates were synthesized and described in Chapter 4 in order to verify that siderophores traverse the outer membrane with large molecules attached. A bisbenzimidazole DNA binding agent was also synthesized and conjugated to the siderophore in order to provide a microbe selective DNA binding agent.; Chapter 5 covers the total synthesis of an analog of the polyamine antibiotic edeine A. This analog was coupled to the siderophore to determine if they can transport large, highly charged molecules through the cellular membrane. These polyamine siderophores can also be utilized to transport anionic molecules such as DNA into the cell. Chapter 6 summarizes the work completed and discusses the possible future directions of this project.