Synthesis and Structure-Activity Relationships of New Antibacterials against Methicillin- Resistant Staphylococcus aureus and Mycobacterium tuberculosis

Before the discovery of antibiotics, bacterial infections were a major cause of human death and suffering. The latter half of the 20th saw the the ‘Golden Era’ of antibiotic discovery, where a large number of new drugs were introduced for routine clinical use, leading to countless lives saved. However, the widespread use (and misuse) of antibiotics has led to an alarming increase in human pathogenic bacteria that have become resistant to many, and in some cases all, antibiotic treatments. Antimicrobial resistance (AMR) is now widely recognised as one of the preeminent challenges facing humanity in the 21st century. Central to our ability to counter AMR is the discovery and development of new antibiotic compounds that act via novel molecular mechanisms. This PhD thesis describes synthetic and medicinal chemistry studies into some new classes of antibacterials that show promising activity against the human pathogens Staphylococcus aureus (Thesis Part A; Chapters 1-4) and Mycobacterium tuberculosis (Thesis Part B; Chapters 5-7).