Novel compounds active against multidrug-resistant highly-prioritized superbugs
Prof. Rosario Musumeci, University of Milano-Bicocca; Prof. Clementina Elvezia Anna Cocuzza, University of Milano-Bicocca; Prof. Andrea Pace, University of Palermo; Prof. Antonio Palumbo Piccionello, IEMEST; Prof. Cosimo Gianluca Fortuna, University of Catania
University of Milano-Bicocca
The continuous evolution of antibiotic resistance mechanisms has forced institutions such as WHO, CDC and ECDC to prioritize bacterial species that must be eradicated with the rapid discovery, development and use of new antibiotics. While it is extremely difficult to discover antibiotics with new mechanisms of action, on the other hand the newer antibiotic classes are increasingly being optimized through the discovery of increasingly active molecules resistant to the development of new resistance mechanisms and with reduced side effects. The research that led to this patent’s family focuses on optimizing one of the most recent classes of antibiotics that have been discovered. The new series of molecules protected here manages to be very active against "SuperBugs" bacteria, so called for their extreme level of antibiotic resistance, such as MRSA, MRSE, PNSSP, VRE, MDR CD, tubercular and non-tubercular MDR mycobacteria.
A new series of oxadiazolyl-oxazolidinonic compounds, effective for use in the treatment of infections caused by both multi-antibiotic-resistant and antibiotic-susceptible high-prioritized pathogens thanks to the improved structures of the compounds obtained by a rationale multidisciplinary approach. Candidates for new antibiotics have specifically been designed and synthesized to overcome all the resistance mechanisms known to date, demonstrating excellent results in terms of antibacterial activity, certified by qualified research institutions such as NIH. The most promising compounds are currently in the preclinical testing phase.
The technology is offered for licensing and further antibiotic co-development.
In vitro activity has been highly proven against several both MDR and susceptible WHO-prioritized pathogens. The researchers are confirming further preclinical development by means of in vivo efficacy and ADME Tox studies.
Italian patent N. 0001416520 granted on 19/06/2015;
US Patent 9862710B2 granted on 09/01/2018;
European Patent EP 2970244B1 granted on 29/05/2019,
US Patent 9920039B2 granted on 20/03/2018;
Japanese Patent JP 6402120B2 granted on 10/10/2018;
Chinese Patent CN105209458B granted on 04/01/2019;
Pending Canadian Patent application n. CA 2907032
Fortuna CG, Bonaccorso C, Bulbarelli A, Caltabiano G, Rizzi L, Goracci L, Musumarra G, Pace A, Palumbo Piccionello A, Guarcello A, Pierro P, Cocuzza CE, Musumeci R (2013). New linezolid-like 1,2,4-oxadiazoles active against Gram-positive multiresistant pathogens. EUR J MED CHEM. (2013); 65:533-45. doi: 10.1016/j.ejmech.2013.03.069.
Fortuna CG, Berardozzi R, Bonaccorso C, Caltabiano G, Di Bari L, Goracci L, Guarcello A, Pace A, Palumbo Piccionello A, Pescitelli G, Pierro P, Lonati E, Bulbarelli A, Cocuzza CE, Musumarra G, Musumeci R. New potent antibacterials against Gram-positive multiresistant pathogens: Effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles. BIOORG MED CHEM. (2014); 15; 22(24):6814-25. doi: 10.1016/j.bmc.2014.10.037.