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Therapeutics & Diagnostics 19-018

Novel bis-amidine compound with antimicrobial activity

Gloved hand holding petri dish with a streaking bacterial pattern.
The antibiotic resistance crisis has been on the rise.

Tech ID



E. Brown
M. Farha
C. MacNair
J. Cote
K. Lee
D. Hung
M. Serrano-Wu
B. Hubbard

Patent Status

PCT application filed

Stage of Research

Proof of concept available


Leigh Wilson
Associate Director, New Ventures


More than 2.8 million antibiotic-resistant infections occur in the US in a year, and more than 35,000 people die. Current antibiotics are proving ineffective as bacteria have developed a myriad of resistance mechanisms. Creating antibiotic adjuvants helps potentiate existing antibiotics and regain the upper hand on bacterial infections. It has previously been found that the anti-fungal drug pentamidine acts as a potentiator of Gram-positive antibiotics against Gram-negative bacteria in vitro and in vivo1. Pentamidine is not, however, an ideal compound due to cytotoxicity, and efforts were required to generate improved analogs.

A team of researchers from McMaster University and the Broad Institute have now developed structurally unique bis-amidine compounds with lower cytotoxicity and improved efficacy. These compounds may be used as potentiators to enhance the activity of antibacterial agents versus previously resistant organisms, particularly pan-resistant Gram-negative bacteria. The researchers tested several pentamidine analogs and have optimized two of the least toxic and effective pentamidine analogs. The compounds have shown in vivo efficacy in a mouse A. baumannii model in combination with novobiocin.


  • Novel antibiotic potentiators that restore Gram-positive antibiotic efficacy against all bacteria, including resistant gram-negative bacteria


  • Enhances gram-positive antibiotics against gram-negative bacteria
  • Potentiators have the flexibility of synergizing with rifampicin, novobiocin, and erythromycin (fractional inhibitory concentration [FIC] index <= 0.5)
  • 1/5 of the human equivalent therapeutic dose of pentamidine and 1/20 of novobiocin was used to rescue mice infected with A. baumannii recognizing the potential of dose-sparing combinations in therapy1.


  1. Stokes, J. M., MacNair, C. R., Ilyas, B., French, S., Côté, J. P., Bouwman, C., Farha, M. A., Sieron, A. O., Whitfield, C., Coombes, B. K., & Brown, E. D. (2017). Pentamidine sensitizes Gram-negative pathogens to antibiotics and overcomes acquired colistin resistance. Nature microbiology2, 17028.

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