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Novel antibiotics with activity against resistant strains

[Category : - HEALTH- Organic Chemistry]
[Viewed 854 times]

The technology includes novel bacterial type II topoisomerases inhibitors as promising new antibiotics with broad spectrum activity against resistant strains and clinical isolates.

Type II topoisomerases are well established therapeutic proteins targeted by fluoroquinolone antibiotics commonly used in clinical practice. Despite the dual-target mechanism of action of fluoroquinolones, the incidence of resistance to these drugs has increased significantly in the last two decades in both Gram-positive and Gram-negative bacteria. The urgent need of new effective antibiotics, following the spread of resistant bacterial strains, has been recognized by WHO as of primary importance. Novel inhibitors of bacterial DNA Gyrase and Topoisomerase IV (NBTIs) have been discovered in the last decade, contemporarily targeting two essential bacterial enzymes and at a different binding site than the fluoroquinolone one, thus potentially overcoming current resistance issues.

The technology relates to 3 families of patent applications disclosing novel antibacterial compounds belonging to NBTI class and showing a broad spectrum of activity against resistant bacterial strains. Described molecules are being developed as new antibacterial agents for the treatment of severe infections caused by both Gram-positive and Gram-negative bacteria, including ciprofloxacin-resistant strains. Of note, compounds show activity against several Staphylococci strains, among which noteworthy MRSA, E. Coli, N. gonorrhoeae, vancomycin-resistant Enterococcus spp, Clostridium difficile, and Acinetobacter baumannii. Selected molecules show good physicochemical characteristics for oral administration and have been tested in animals for efficacy studies. The asset also includes derivatives among which physiologically acceptable addition salts.

Selected novel antibacterial compounds are able to simultaneously inhibit two essential enzymes in many bacterial species at a different binding site compared to fluoroquinolone antibiotics, thus showing activity against Gram-positive and Gram-negative resistant strains and potentially overcoming resistance occurrence.

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