University of Notre Dame Du Lac

Derong Ding

Shahriar Mobashery

Mayland Chang

Sebastian Testero

Erika Leemans

Edward Spink

Marc Boudreau

infection (CDI) is a public health threat that results in 14,000 annual deaths in the United States. Challenges involve the production of CDI spores that can remain dormant for years and the production of toxins that damage the gut. Current therapies for CDI include vancomycin and metronidazole, but neither inhibits spore or toxin production. Thus, recurrence of infection occurs in 25% of patients and there are no antibiotics that are effective for multiple recurrences. We describe oxadiazoles with activity against, including the highly virulent NAP1/027 strain with increased production of toxins A and B, as well as the additional binary toxin. Oxadiazole 2 is poorly absorbed, thus advantageously achieving high concentrations in the gut. The compound targets peptidoglycan synthesis and inhibits vegetative cells, spores, and toxin production.

Compounds for the treatment ofinfection

Compounds for the treatment of clostridium difficile infection

The invention provides a newly discovered oxadiazole class of antibiotics. The oxadiazoles impair cell-wall biosynthesis and exhibit activities against the Gram-positive bacteria such as the bacterium, including methicillin-resistant(MRSA) and vancomycin-resistant and linezolid-resistant. For example, 5-(1H-indol-5-yl)-3-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,2,4-oxadiazole (antibiotic 75b) was efficacious in a mouse model of MRSA infection, exhibiting a long half-life, a high volume of distribution, and low clearance. Antibiotic 75b antibiotic is bactericidal and is orally bioavailable. This class of antibiotics can be used as a therapeutic agent against infections by Gram-positive bacteria such as MRSA.

Non-beta lactam antibiotics

Growing community of inventors

South Bend, IN, United States of America

Derong Ding