Innovative compound with anti-MRSA qualities may help develop new class of antibiotics

Dec 1 2015

With global health services increasingly worried about the rise of antibiotic resistant diseases, researchers at Maynooth University have discovered a compound whose anti-MRSA qualities pave the way for the development of a new class of antibiotics. The new research is published today in the internationally renowned journalBioorganic and Medicinal Chemistry Letters. The findings mark the culmination of three years of work on the part of the team led by Dr John Stephens, Maynooth University Department of Chemistry, in collaboration with Dr Kevin Kavanagh, Maynooth University Department of Biology.

According to recent studies, on any given day one in 18 hospitalised patients are suffering from healthcare associated infections, with MRSA and E. coli responsible for 64% of cases. Doctors struggling with these infections are confronted with the increased prevalence of antibiotic resistant strains, but this represents only part of the problem. Of the antibiotics used today, almost all of them belong to classes discovered before the 1980s and this research was motivated by the urgent need to identify and synthesise new antibiotic classes.

Commenting on this discovery, Dr John Stephens observes:

As today’s infections develop increasing resistance to the antibiotics of the past, there is an urgent need for researchers to develop new therapeutics. Without this action, we are seriously at risk of entering a post-antibiotic world where common and traditionally minor infections could once again prove fatal. Discovering the antibacterial properties of our lead compound, the highly active quinoline thiourea, at Maynooth University is a significant first step. With further research and development, it has the potential to pave the way for a new class of antibiotic.

The team employed a “building block” approach to their search for new anti-bacterial compounds. This entailed considering compounds that have components found in established antimicrobial agents or components that have the potential to enhance biological activity. A number of these compounds were chosen and evaluated for their effectiveness against S. aureus and E. coli.

This evaluation identified the lead quinoline thiourea compound, what the Pharmaceutical Industry would term a “small molecule”, which exhibited remarkable anti-MRSA activity that was comparable to antibiotic agents currently used as last resort drugs in the treatment of drug resistant infections. This prompted further study into the quinoline thiourea, and its derivatives, in order to help understand its impressive biological activity and to identify the functional groups responsible for this activity.

Following an extensive study, relating compound structure to anti-bacterial activity, the lead quinoline thiourea was confirmed as having significant potential as a new anti-bacterial agent class. Further testing was the then required to determine if the quinoline thiourea presented any immediate toxicity issues and to investigate its selectivity in targeting bacteria.

A toxicity study was performed on a number of compounds, including the lead quinoline thiourea, using the larvae of the greater wax moth. Tested at a range of concentrations, the compounds displayed a 100% survival rate.  Furthermore, the larvae were also seen to proceed along their normal development pathway. These results indicate that not only were the compounds non-toxic to the larvae but they also did not appear to interfere with their development.

Maynooth University President Professor Philip Nolan noted:

The problem of antibiotic efficacy has been a vitally important issue in medical science for decades, so this is an exceptionally exciting development that could have an impact on countless lives for years to come.  Maynooth University’s research tackles the big, difficult issues, and it is a great pleasure to see our Departments of Chemistry and Biology taking a leadership position on such an important topic.