<p>Quorum sensing is a bacterial signaling system that involves the synthesis and
subsequent detection of small signal molecules called autoinducers. The main autoinducer in
gram-negative bacteria are acylated homoserine lactones (AHLs), produced by LuxI autoinducer
synthase enzymes and detected by LuxR autoinducer receptors. Quorum sensing allows for
changes in gene expression resulting bacterial behavior in a coordinated, cell-density
dependent fashion. Some of the behaviors controlled by quorum sensing involve pathogenesis,
making quorum sensing signaling a target to develop new antibacterial agents. Here we
describe the design and synthesis of transition-state analogs of the autoinducer synthase
enzymatic reaction and the evaluation of these compounds as inhibitors of the synthase CepI.
One such compound potently inhibits CepI and constitutes a new type of inhibitor against this
underdeveloped antibacterial target.</p>
Design and Synthesis of a Triazole‐based Small Molecule Library for the Inhibition of Bacterial Quorum Sensing
