Development of the diaryl ether scaffold as inhibitors of EcDsbA using a fragment-based approach

Antibiotic resistance is becoming a global health threat and drugs with novel mechanisms of action are required to provide new approaches to the treatment of bacterial infections and to combat resistance. This thesis examines the development of a series of novel anti-bacterial compounds targeting the bacterial enzyme DsbA. DsbA is required for the correct folding of many proteins that the bacteria use to establish an infection. Inhibitors of DsbA have the potential to “disarm” bacteria and thereby render them avirulent. As such DsbA inhibitors would represent a novel therapeutic approach to the treatment of bacterial infections.