Poster Presentation The 43rd Lorne Conference on Protein Structure and Function 2018

Synthesis of novel 1,2,5-oxadiazoles and evaluation of their antibacterial action   (#154)

Rebecca M Christoff 1 , Gerald L Murray 2 , Kostoulias P Xenia 2 , Deady W Leslie 1 , Peleg Y Anthony 2 , Belinda M Abbott 1
  1. Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia
  2. Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia

The rise of multidrug resistant bacteria is becoming a significant health threat worldwide. In 2013 the Centers for Disease Control and Prevention (CDC) reported that there are 2,000,000 infections and 23,000 deaths caused by multidrug resistant pathogens each year in the United States alone,1 highlighting the importance of this issue. One bacterial pathogen of interest is Acinetobacter baumannii. Recently identified by the World Health Organisation (WHO) in critical need for new antibiotics, A. baumannii is a gram negative organism that may be responsible for pneumonia, meningitis, blood stream, urinary tract, skin and wound infections. In 2008, eleven compounds were identified by high throughput screening (HTS) as inhibitors of BasE, a key enzyme involved in the iron acquisition pathway found in Acinetobacter baumannii.2 Interested in the activity these compounds in vivo, five of the reported HTS hits were synthesised and evaluated as inhibitors of A. baumannii. A further library of novel 1,2,5-oxadiazole derivatives were developed from the most promising lead and their antibiotic activity determined.

  1. CDC, Antibiotic Resistance Threats in the United States, USA, 2013.
  2. J. Neres, D. J. Wilson, L. Celia, B. J. Beck and C. C. Aldrich, Biochemistry, 2008, 47, 11735-11749