Novel Antimicrobials

About

The USP lies in the mode of action (novel and unexploited) of these materials. The agents modify the chemical composition of the membrane and do not target any metabolic pathways. Membranes are an interesting target – they are ubiquitous in bacteria, and also found in enveloped viruses (such as Ebola). These agents therefore have the potential to be tuned for either broad or narrow spectrum activity. The agents are “pharma-friendly”, i.e. acceptable by Lipinski rules. The mode of action exploits chemical processes that we have identified in Durham, whereby some functional groups are reactive towards chemical components of the membrane, leading to their chemical transformation within the membrane. This transformation can be detrimental to cell viability. There is chemical selectivity within this process (some functional groups are reactive, others are not). We are undertaking research to establish a framework for understanding the reactivity (at an academic level). At an application level, we have screened ~80 compounds to date for this activity. Screens have been conducted in vitro (using liposome models) and in vivo using a small selection of G+ and G- organisms, as well as screening for adverse activity using hemolysis assays. Given that we have only tested a small number of compounds, initial results are encouraging – we have a handful of compounds that have acceptable activity in microorganisms and low activity in hemolysis assays.