19-018
E. Brown M. Farha C. MacNair J. Cote K. Lee D. Hung M. Serrano-Wu B. Hubbard
PCT application filed
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.