Development of new antibiotics: Synthesis of innovative aminoacylated sulfonamide nucleosides and mupirocin analogues as aminoacyl-tRNA-synthetase inhibitors

The alarming spread of bacterial resistance to existing antibiotics is a serious global health threat. As a result, there is an urgent need for new antibiotics which preferably act on new cellular targets that are essential for the survival of pathogens. The toxicity, selectivity, bioavailability in patients, the serum stability and, in particular, the bacterial uptake are important challenges in the development of new antibiotics.
The last two decades, aminoacyl-tRNA synthetases (aaRSs) were identified as a clinically validated target for the development of antimicrobial agents. Because aaRSs are retained in all living organisms, but with extensive polymorphisms, a part of the challenge exists in the development of an appropriate lead compound with good specificity for particular species, so that an optimal therapeutic ratio can be achieved.

The ultimate goal of this project is to synthesize aaRS inhibitors with a better therapeutic index in order to provide a solution to the problems outlined above (including the toxicity, selectivity and bacterial uptake) that emerge in the development of new antibiotics.
We want to achieve this goal (1) starting from a new set of aminoacylated sulfonamide nucleosides and (2) on the basis of new mupirocin analogues.