Antibiotic drugs targeting lipoteichoic acids biosynthesis

Marshall, Brandon 2025. Antibiotic drugs targeting lipoteichoic acids biosynthesis. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

This thesis describes the development of an antibacterial compound first identified in a high throughput screen with efforts to improve its antibacterial potency, metabolic stability, and attempts to synthesise analogues that function as biological probes to study the mode of action and pharmacokinetics of the compound. Antimicrobial resistance is considered a major threat to healthcare and is responsible for hundreds of thousands of deaths per year globally, therefore research to combat the spread and evolution of multi-drug resistant bacteria is of great importance and interest. This work is made up of 5 parts, with aims to: First in chapter 2, we attempt to increase potency against a variety of pathogenic bacteria and study the effects of the compound on the biochemistry of the bacteria. Second, in chapter 3 we attempt to synthesise more stable analogues and study the structure-activity relationships of the analogues. Third, in chapter 4 we evaluate the stability in blood serum. Fourth, in chapter 5 we assess the physiochemical properties of the compound and analogues. Finally, in chapter 6 we make efforts towards the synthesis of analogues that would allow for protein tagging (to determine the mode of action) and Positron Emission Tomography (to determine pharmacokinetic properties) While the small molecules that have been produced by the research in this thesis are far from a clinical trial, they show great promise as they appear to have a novel mode of action, show favourable stability in human plasma, low toxicity in a cell health screen, reasonable predicted physiochemical properties, and a low potential for resistance in laboratory experiments. [1]

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Chemistry
Date of First Compliant Deposit:	14 April 2026
Last Modified:	14 Apr 2026 14:30
URI:	https://orca.cardiff.ac.uk/id/eprint/186363

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