Synthetic Investigations into Small Molecules with Antibacterial Potential Public

Abstract

Due to the rise of resistant bacteria and persister cell populations, a new demand for novel antibiotics has arisen to combat these strains before they lead to a severe infection or even death. In recognizing this issue, our work focuses on two different mechanisms of action to kill resistant and persistent bacteria. The first is membrane perturbation in which the bacterial membrane is perturbed,  ultimately leading to cell death. The second mechanism is that of metallophores, such as siderophores or chalkophores, which can utilize metallophore uptake machinery to trick the bacterial cell for uptake and in turn, provide an opportunity to lead to the cells’ ultimate destruction. From these mechanisms, two small molecules were identified and synthesized to analyze their potential as antimicrobial agents. The first being CD437, a synthetic retinoid that previously displayed activity through membrane perturbation. The other being SF2768 which showed promise as a bacterial chalkophore. This work will further elucidate the potential of these molecules and outline the synthetic methods used to achieve them.

Table of Contents

Table of Contents

 

Chapter 1- Introduction to Bacterial Resistance, Persistent Mechanisms, and Antimicrobial Compounds ………………………………………………………………………………………1

1.1- Membrane Perturbation……………………………………………………………………..3

1.2- Metallophores………………………………………………………………………………..4                                                                                                     

 

Chapter 2- CD437…………………………………………………………………………………6

2.1- Introduction………………………………………………………………………………….6

2.2- Synthetic Methods…………………………………………………………………………...8

2.3- Results and Analysis…………………………………………………………………………11

 

Chapter 3- SF2768……………………………………………………………………………….14

3.1-Introduction……………………………………………………………………………..….14

3.2- Synthetic Methods………………………………………………………………………….16

3.3- Results and Analysis…………………………………………………………………………18

Chapter 4- Final Remarks………………………………………………………………………...20

 

Supplemental Information………………………………………………………………………21

 

References………………………………………………………………….……………………42

Figures

Figure 1……………………………………………………………………………………………7

Figure 2…………………………………………………………………………………………..15

Figure 3………………………………………………………..…………………………………17

Scheme 1…………………………………………………………………………………………..9

Scheme 2…………………………………………..………………………………………………9

Scheme 3…………………………………………………………………………………………10

Scheme 4…………………………………………………………………………………………10

Scheme 5…………………………………………………………………………………………17

Scheme 6…………………………………………………………………………………………18

Scheme 7…………………………………………………………………………………………18

Table 1……………………………………………………………………………………………12

Table 2……………………………………………………………………………………………13

About this Honors Thesis

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School	Emory College
Department	Chemistry
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Chemistry, Organic
Mot-clé	Synthesis
Committee Chair / Thesis Advisor	Wuest, William M., Emory University
Committee Members	Roth, Connie B. , Emory University Himes, Richard A. , Emory University

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