Infectious disease currently accounts for approximately one-third of the annual worldwide mortality. In the past two decades, increasing rates of emergence of drug resistant, and multiple-drug resistant microbial infections have served to underscore the urgent need to develop new antibiotics that are both selective and safe. One potential target for novel antibiotics is the microbe specific enzyme 5' Methylthioadenosine /S-adenosylhomocysteine nucleosidase (MTN). This enzyme has been implicated in playing a central role in nutrient salvage and in the synthesis of bacterial quorum sensing molecules that govern processes such as drug resistance, biofilm formation, and the expression of virulence. As part of this work, we have investigated the synthesis of two classes of novel non-hydrolysable nucleoside analogs which could serve as potential MTN inhibitors. The compounds developed in this study are derived from either the cyclic amino acid L-proline or from di-substituted urea compounds.

Progress towards the development of novel MTN-specific inhibitors to interrupt bacterial signaling processes