Lipophosphonoxins, new antibiotics overcoming bacterial resistance

Rejman D., Pohl R., Bartůněk P., Ribeiro Pombinho A. J., Krásný L., Látal T.

Snímek2Challenge  

The advantages offered by antibiotics in the treatment of infectious diseases are endangered due to the increase in the number of antibiotic-resistant bacterial strains. This reduces the efficiency of antibiotic treatments and poses a serious health and economical problem. Currently, the need for novel antibiotics is becoming increasingly apparent.

Technology

This invention describes novel compounds that exhibit significant antibacterial activity in particular against gram-positive bacteria including resistant strains. Advantage of these compounds consists in simple synthesis and their modular structure allowing for further optimization of their biological properties. Beside pharmacological application, diagnostic use of compounds is under development.

Commercial Opportunity

The project is offered for co-development, licensing and research collaboration.

Development Status

Synthetic methods for preparation of gram amounts of the title compounds have been developed. Antibacterial activity of a series of compounds has been determined using standard microdilution method (in vitro). Cytotoxicity of the compounds has been determined (in vitro, erythroid progenitor cells). It was also determined that the most promising compounds are not genotoxic. The mechanism of action of these compounds has been studied intensively for the last two years. There are strong evidences that these compounds selectively disrupt bacterial cell membrane. We were able to produce resistant strain against one of two selected most active lipophosphonoxins but we were not able to form resistant strain against the other compound. MTD tests in mouse models are currently under way.

Development of selective growth media utilizing lipophosphonoxins as an antibacterial supplement is currently under way.

Patent Situation

EP and Czech Patent Application has been filed in 2011. Testing of novel derivatives is currently under way, new patent application is expected.

IP owners

Institute of Organic Chemistry and Biochemistry AS CR, v.v.i.
Institute of Molecular Genetics AS CR, v.v.i.
Institute of Microbiology AS CR, v.v.i.
Trios, spol. s r.o.

Further Reading

Rejman D., et al. Lipophosphonoxins: new modular molecular structures with significant antibacterial properties. J Med Chem, 2011 Nov 24; 54(22):7884-98