A New Class of Antibiotics: Naturally-occurring Chrysophaetins and Their Analogues

This invention, offered for licensing and commercial development, relates to a new class of naturally occurring antimicrobial compounds called Chrysophaetins, and to their synthetic analogues. Isolated from an alga species, the mechanism of action of these compounds is through the inhibition of bacterial cytoskeletal protein FtsZ, an enzyme necessary for the replication of bacteria. FtsZ is responsible for Z-ring assembly in bacteria, which leads to bacterial cell division. Highly conserved among all bacteria, FtsZ is a very attractive antimicrobial target.

The chrysophaetin exhibits antimicrobial activity against drug resistant bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE), as well as other drug susceptible strains. The general structure of the natural compound is shown below:



The inventors are working on a synthetic route for the compound and analogs. They have made progress and now have two halves of the molecule. These will be further dimerized to produce a synthetic chrysophaentin. It is expected that the analogues will show similar antimicrobial activity to the natural products and will utilize the same mechanism of action.

The market potential for the disclosed compounds is huge ($24 billion in 2008) due to the very limited number of new antibiotics developed in recent decades and the increased epidemic of infectious diseases. In fact, infectious diseases are the leading cause of death worldwide. In the United States alone, more people die from MRSA than from HIV (Journal of the American Medical Association, 2007) and more than 90,000 people die each year from hospital acquired bacterial infections (Centers for Disease Control). A development of new drugs with distinct mechanism of action and efficacy against resistant bacterial strains may therefore be commercially attractive. CRADA Opportunity: The National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Bioorganic Chemistry, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the chrysophaentin antibiotics. Please contact Marguerite J. Miller at 301-451-3636 or millermarg@niddk.nih.gov for more information.

Source: http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2123

Georgina Grenville Gina Carano Gina Gershon Gina Philips Giuliana DePandi