Two novel ruthenium antimicrobial compounds to treat Gram-negative, pathogenic, multi-drug resistant infections.

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Antimicrobial resistance (AMR) is globally responsible for 700,000 annual fatalities. Failure to address this issue by 2050 could result in 10 million deaths per year, costing the global economy £66 trillion. To put this into context, the predicted death rate for cancer will be 8.2 million by the same year. As current antibiotics fail minor injuries, like a scratch on the knee, could soon become fatal. To address this emergency, the World Health Organisation (WHO) has called for novel methods to treat antibiotic resistant infections. Our team are directly answering this call, in line with the UK Government's 20-year vision to control and contain AMR by 2040\. As part of a highly skilled team, we have developed two novel antimicrobial compounds to treat these extensively-drug resistant infections where other antibiotics are failing.The compounds exhibit comparable activities to clinical antibiotics but, crucially they retain this high activity against drug-resistant bacteria, including bacterial strains The WHO has declared as critical priorities for new treatments. The complexes themselves have a modular synthesis. Like Lego, we can exchange the " building blocks" of our current leads to make a whole series of potential drugs. Both compounds have been found to be non-toxic to human cell lines and in living wax moth larvae. In addition, both compounds cleared a fatal infection from the larvae using a single dose.This project will directly build upon our preclinical data, accelerating the technology's development, reducing our time to market. This will increase the probability of the compounds successfully reaching the clinic. Final activity and toxicity studies will be carried out in cell lines (in a test tube/culture dish) and data from these studies will be used to facilitate co-development discussions. To build upon the previous living model data, the adsorption, distribution, metabolism and excretion properties of the drugs will be studied in a mouse model. In addition, the compounds toxicity levels, and their ability to clear a pathogenic _E. coli_ thigh infection will be studied. The mice will be closely monitored in the studies to record any effects of the compounds. These experiments will de-risk the technology, allowing its progression onto a medium animal pre-clinical model.Our compounds explore a new area of antimicrobial chemistry, their structures are radically different to any antibiotics in the clinic. This will reduce the likelihood of resistance emerging, increasing the capability to treat infections and improve patient quality of life.