Oral Presentation 11th Annual Conference of the International Chemical Biology Society 2022

Synthesising conjugate drugs to kill nasty bugs: Combining antibiotics to fight antimicrobial resistance. (#22)

Anthony Verderosa 1 2 , Vito Ferro 3 , Mark Blaskovich 1 2
  1. Centre for Superbug Solutions, Australian Infectious Diseases Research Centre, Institute of Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia
  2. UQ, Brisbane, QLD, Australia
  3. School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia

The world is running out of antibiotics, with antimicrobial resistance (AMR) a major global threat with devastating implications. If left unaddressed, by 2050, it is estimated the cumulative impact of AMR on Australia alone will be >$280 billion, with many thousands of deaths. New drugs are urgently needed, but the World Health Organisation reports that a “lack of innovation in developing new antibiotics undermines efforts to combat drug-resistant infections”. To address the urgent need for new antibiotics, we have synthesised an advanced platform of bespoke derivatised antibiotics, covering all major antibiotic classes. The facile addition of an azide handle to these antibiotics, coupled with an alkyne linker, has allowed us to quickly couple different antibiotics together. These antibiotic-antibiotic hybrids combine the power of two distinct mechanisms of action to create a powerful series of dual-acting drugs. Our preliminary results have demonstrated improvements in activity between 4-fold and 100-fold, compared to the parent compounds against resistant bacterial pathogens. We expect these new conjugate drugs to eventually form an essential part of the armamentarium in the fight against AMR.