Date of Award

5-2010

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program

Pharmaceutical Sciences

Research Advisor

Richard Lee, Ph.D.

Committee

James Bina, Ph.D. Isaac Donkor, Ph.D. Wei Li, Ph.D. Duane Miller, Ph.D

Abstract

There is an ever increasing need to develop new antimicrobial agents with novel mechanisms of action. These new agents will help to combat the steady rise of antibiotic-resistant bacteria which are becoming more and more difficult to treat due to the dwindling number of antibiotics available to treat such organisms. This body of work brings to light the many ways in which medicinal chemistry plays a vital role in the discovery of novel antimicrobial agents. Chapter 1 is an introduction into antimicrobial agents. It provides a brief history of the discovery of antimicrobial agents, and delves into reasons why new agents are urgently needed. It also examines the recent antimicrobial agents approved by the Food and Drug Administration for use in the United States, and looks into the current antimicrobial drug pipeline. Chapter 2 explores the current therapy regime for combating tuberculosis and expresses the need for novel agents in this arena. It also shows how current medicinal chemistry techniques are being utilized to develop a novel class of potential anti-tuberculosis agents with novel mechanisms of action. Chapter 3 discusses the treatment of gram-negative bacterial infections with novel hybrid antimicrobial agents. These agents afford current antimicrobial agents, which have difficulty penetrating the gram-negative cell wall, a way into the gram-negative cell in order to exert their intended mechanism of action. This chapter explores the rationale and design behind the making of such agents. Chapter 4 provides an overview of the work detailed in the dissertation; as well as future directions that will help further the scope of these projects.

DOI

10.21007/etd.cghs.2010.0035

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