There is a pressing clinical need for effective new agents to combat bacterial infection. In particular, Clostridium difficile can be problematic to treat. Cases of illness attributable to C. difficile have doubled in the last two years as a result of strains of this bacterium emerging that are resistant to the commonly used antibiotics.

Historically, antibiotics such as Opt-80, Vancomycin, and Metronidazole have been used to treat C. difficile infection. However, Metronidazole is indiscriminate in its antibacterial activity and will attack various gut colonizing bacteria, exacerbating the life threatening effects of C. difficile-associated diarrhoea. Vancomycin is more effective but many strains of C. difficile are resistant to treatment with this antibiotic.

A family of compounds that are active against C. difficile and other bacterial pathogens but which are inactive against the benign gut flora and to which existing bacterial strains have no resistance would therefore be highly desirable.

Scientists at Aston have developed a range of novel compounds that are active against C. difficile, but which do not affect other gut flora and to which existing clinical strains of C. difficile do not show resistance.

It is known that the enzyme dihydrooroate dehydrogenase (DHODase) isolated from Clostridium oroticum can be inhibited. However, the treatment of whole organisms using inhibitors of DHODase has not been considered, and the study of DHODase derived from C. difficile and other Gram positive bacteria has been limited.

The Aston group have now synthesized a range of DHODase inhibitors and found them to be excellent inhibitors of C. difficile activity.