Graduation Year

2011

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Chemistry

Major Professor

Edward Turos

Abstract

Antibiotic resistance is a particularly critical health concern and has increased dramatically over the past two decades. For over a decade the Turos laboratory has been designing small molecules to target pathogenic microbes such as Staphylococcus aureus and the resistant variants like methicillin-resistant Staphylococcus aureus (MRSA). Previously, N-thiolated Β-lactams, N-thiolated 2-oxazolidinones and aromatic disulfides that were synthesized in Dr. Turos' lab have shown strong activity against these bacteria. The present work describes the synthesis and antimicrobial activities of a related structural class called S,S'-heterosubstituted disulfides. For ages, sulfur (elemental) has been used as an antibacterial for controlling infestation and bacterial diseases. This is the starting point of this thesis. Chapter 1 discusses the various sulfur-containing antibiotic compounds and the importance of sulfur compounds to exhibit inhibitory activity against disease-causing pathogens. Also in this introductory chapter, the different sulfur functionalities and their respective modes of action were presented. The synthesis and the antimicrobial activities of the title compounds are described in chapter 2. S,S'-heterosubstituted disulfides were found to possess inhibitory activities against Staphylococcus aureus, methicillin resistant Staphylococcus aureus (MRSA), Francisella tulerensis and the fungi Candida albicans. From the bacterial viability assay and the trypan staining assay, these compounds were found to be bacteriostatic and fungistatic, and these structurally-simple disulfides may serve as new leads to the development of effective antibacterials for drug-resistant staph infections.

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