Since their discovery, antimicrobial compounds have been vital for the treatment and prevention of disease; making many previously fatal diseases treatable or at worst, manageable conditions. The inappropriate use of these compounds has led to the rapid development of resistance mechanisms within bacteria to the majority of compounds currently marketed. A recent UK governmental review predicted that by 2050 global deaths caused by antimicrobial resistant bacteria will outnumber those attributed to cancer [1]. As new resistance mechanisms emerge and resistance within microbial populations increases, so does the need to further understand the molecular basis of resistance, develop new antimicrobial molecules and use better strategies to manage their use [2]. In response to this, we discovered a novel class of antimicrobials and have created 50 structurally related members of this class [3-6]. We sought to understand the structure-activity relationships which will result in the determination of the mode of action of these molecules. Consequently, each variant was screened against Staphylococcus aureus and Escherichia coli and the minimum inhibitory concentration was calculated for effective compounds. This will enable us to identify predictive tools that will aid the synthesis of the next generation of these novel therapeutic molecules. We will present our latest findings in the ongoing analysis of the antimicrobial activity for each variant of this new class of antimicrobial compound. In addition, we will discuss the insights provided by the detailed structure-function analysis. This project is in collaboration with Public Health England and NHS East Kent Trust.


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