Design, Synthesis, and Evaluation of Diarylurea Complexes and Next-generation Inhibitors of Bacterial MTN

Infectious disease, which currently accounts for approximately one-third of the annual worldwide mortality, presents a real and pressing threat to the health and wellbeing of the global population. This challenge is compounded by the increasing rate of emergence of drug resistant and multiple-drug resistant microbial infections, which further underscores the continued need to develop new antibiotics that are both selective and safe. One potential target for antimicrobial therapies is 5' Methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTN), an enzyme that is unique to microorganisms and which is known to play a central role in processes associated with bacterial quorum sensing such as drug resistance, biofilm formation, and the expression of virulence. As part of this project, we have explored the ability of a series of N,N’-diarylurea complexes – identified through in silico screening techniques – to function as next-generation inhibitors of MTN. The activity of the complexes developed in this study against both protein isolates and microorganisms will be presented.