Development of Novel Antibacterial Agents through the Design and Synthesis of Aminoacyl tRNA Synthetase (AaRS) Inhibitors

Abstract

Aminoacyl tRNA synthetases are valuable targets for antibiotic development as they have a fundamental role at a cellular level during the translation process of the genetic code. Mupirocin (Bactroban ®) is an approved isoleucine tRNA synthetase inhibitor which is used for the treatment of methicillin resistant Staphylococcus aureus (MRSA). High and low level of mupirocin resistance has been demonstrated in most S. aureus isolates due to acquired plasmid-mediated mupA, which encodes a novel IleRS and mutation, respectively. Thus, the design of multitarget aminoacyl tRNA synthetases inhibitors could be an effective way to make significant reductions in the biological fitness of bacteria leading to a reduction in drug resistant microorganisms.