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Cationic steroids as antimicrobial agents

Description:

Brief Description: Antibacterial and anti-inflammatory activity of a cationic disubstituted dexamethasone-spermine conjugate

 

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Technology:

 

            The emergence of antibiotic-resistant bacteria is a rising health crisis that requires the development of new antibacterial agents.  Cationic steroids disrupt bacterial membranes via physical and chemical mechanisms that prevent bacteria from evolving resistance to membrane-permeabilizing cationic amphipathic molecules.  Researchers in the Diamond lab have identified a new method of use for the cationic corticosteroid disubstituted dexamethasone spermine (D2S) as an anti-bacterial agent for both Gram-positive (e.g. MRSA) and Gram-negative (e.g. E. coli) organisms that can cause life-threatening situations, particularly in hospital-based infections.  D2S has been demonstrated to exhibit antibacterial activity against clinical isolates of Staphylococcus aureus and Pseudomonas aeruginosa from cystic fibrosis sputa and biofilms.  Furthermore, D2S enhances S. aureus susceptibility to antibiotics, including amoxicillin, tetracycline, and amikacin.

 

 

From Bucki et al, 2010.  Bactericidal activity of dexamethasone (filled black triangle), spermine (open triangle), dexamethasone-spermine (filled diamond), and D2S (open diamond) against P. aeruginosa.

 

 

Advantages:

·         Small cationic steroid

·         Resists proteolytic activity of pepsin

·         D2S maintained in ascites, cerebrospinal fluid, saliva, and bronchoalveolar lavage fluid

·         Enhanced S. aureus susceptibility to antibiotics

·         Adaptable to large-scale manufacturing

 

Applications:

·         Antibacterial development

·         Anti-inflammatory agent

 

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Stage of Development:

·         Proof-of-concept in vitro and in vivo mouse data

 

Intellectual Property:

USSN 9,180,132

 

Reference Media:

Myint M. et al.  Bioorg Med Chem Lett, 2015, 25(14), p. 2837-2843.

Bucki R. et al. Antimicrob Agents Chemother, 2010, 54(6), p. 2525-2533.

Fein D.E. et al.  Mol Pharmacol, 2010, 78(3), p. 402-210.

 

Desired Partnerships:

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Patent Information:
For Information, Contact:
Joshua Jeanson
Associate Director, SEAS/SAS Licensing Group
University of Pennsylvania
jeanson@upenn.edu
Inventors:
Paul Janmey
Scott Diamond
Keywords: