Combatting antimicrobial resistance through targeting bacterial cell division

This project aims to develop novel antibiotics targeted to the bacterial cell-division protein, FtsZ. This protein is an attractive target for antimicrobial drug discovery as it plays a pivotal role in prokaryotic cytokinesis, is essential for cell survival and is widely conserved in bacteria. Some of our current lead compounds include FtsZ inhibitors with potent activity against multidrug resistant organisms, such as methicillin resistant S. aureus (MRSA), and with the ability to restore the activity of beta-lactam antibiotics. Further work on this project will deliver desperately needed lead compounds to supplement the clinical trial pipeline for antimicrobials against multidrug resistant pathogens that could additionally restore activity of the critically important beta-lactam antibiotics.

This project was funded by the China-Australia Centre for Health Sciences Resaerch

Papers relating to this project

  1. Chai WC, Whittall JW, Song D, Polyak SW, Ogunnyi AD, Wang Y, Bi F, Ma S, Semple SJ, Venter H* (2020) Antimicrobial action and reversal of resistance in MRSA by difluorobenzamide derivatives targeted at FtsZ. Antibiotics, 9(12), 873
  2. Bi F, Song D, Zhang N, Lui Z, Gu X, Hu C, Cai X, Venter H, Ma S (2018) Design, synthesis and structure-based optimization of novel isoxazole-containing benzamide derivatives as FtsZ modulators. Eur J Med Chem, 159:90-103. DOI: 10.1016/j.ejmech.2018.09.053
  3. Liu J, Ma R, Bi F, Zhang F, Hu C, Venter H, Semple SJ, Ma S (2018) Novel 5-methyl-2-phenylphenanthridium derivatives as FtsZ-targeting antibacterial agents from structural simplification of natural product sanguinarine. Bioorg Med Chem Lett, 28(10):1825-1831.
  4. Liu F, Venter H, Bi F, Semple SJ, Liu J, Jin C, Ma S (2017) Synthesis and antibacterial activity of 5-methylphenanthridium derivatives as FtsZ inhibitors. Bioorg Med Chem Lett. 27:3399-3402.
  5. Bi F, Guo L, Wang Y, Venter H, Semple SJ, Liu F, Ma S (2017) Design, synthesis and biological activity evaluation of novel 2,6-difluorobenzamide derivatives through FtsZ inhibition. Bioorg Med Chem Lett. 27:958-962.
  6. Qiang S, Wang C, Venter H, Li X, Wang Y, Guo L, Ma R, Ma S (2016) Synthesis and biological evaluation of novel FtsZ-targeted 3-arylalkoxy-2,6-difluorobenzamides as potential antimicrobial agents. Chem Biol Drug Des, 87:257-64.