A new compound sets its sights on C. diff

WEST LAFAYETTE, Ind.—Clostridioides difficile, also known as C. diff, is a leading cause of health care-associated infection in the U.S. Two antibiotics, vancomycin and fidaxomicin, are approved by the U.S. Food and Drug Administration for the treatment of C. diff, but even these therapies suffer from high treatment failure and recurrence.

Purdue University researchers have advanced novel compounds they developed to help treat patients with C. diff, which is one of four bacteria considered an urgent threat by the Centers for Disease Control and Prevention. Their work was published in an article in the Journal of Medicinal Chemistry.

“Our compounds have several advantages, including ultrapotent activities with minimum inhibitory concentration values as low as 0.003 μg/mL,” said Herman O. Sintim, the Drug Discovery Professor of Chemistry at Purdue University. “Our compounds also do not kill good bacteria at concentrations that kill C. diff and performed significantly better than current antibiotics in preventing recurrence. These are significant advantages for patients dealing with this difficult bacterial infection.”

“Trifluoromethylthio containing N-(1,3,4-oxadiazol-2-yl) benzamides displayed very potent activities (sub-µg/mL minimum inhibitory concentration (MIC) values) against Gram-positive bacteria,” notes the article abstract. “Here, we report remarkable antibacterial activity enhancement via halogen substitutions, which afford new anti-C. difficile agents with ultrapotent activities (MICs as low as 0.003 µg/mL (0.007 µM)) that surpassed the activity of vancomycin against C. difficile clinical isolates.”

“The most promising compound in the series, HSGN-218, was non-toxic to mammalian colon cells and is gut restrictive. In addition, HSGN-218 protected mice from CDI [C. difficile infections] recurrence,” the article continues. “Not only does this work provide a potential clinical lead for the development of C. difficile therapeutics but also it highlights dramatic drug potency enhancement via halogen substitution.”

Sintim pointed out that HSGN-218 has been shown to be one of the most potent compounds ever produced for use against C. diff.

“This is part of our work to create new solutions to treat diseases and infections, which are resistant to current treatment options,” added Sintim, who is also a member of the Purdue University Center for Cancer Research and the Purdue Institute for Drug Discovery. “This work provides a potential clinical lead for the development of C. diff therapeutics and also highlights dramatic drug potency enhancement via halogen substitution.”