Bacteria communicate with each other by producing and detecting small molecules in a process known as quroum sensing (QS). QS enables the bacteria to adjust gene expression to coordinate their behavior in a cell-density dependent manner. Biofilms are associated with majority of bacterial infections and the inhibition of QS can lead to the inhibition of biofilm formation thereby reducing infection or enhancing the effect of traditional antibiotics. We envisioned the development of functionalized cinnamates as QS inhibiting antimicrobial agents. Application of the Baylis-Hillman reaction provides allylic alcohols and amines in a one-step transformation and facilitates the generation of a large library of structurally diverse scaffolds. Employing this strategy, we prepared a series of α-piperazinylmethylcinnamates. Biological evaluation of these compounds enabled the identification of a new structure class of drug-like reversible inhibitors of LasR quorum sensing in <i>Pseudomonas aeruginosa.</i> This presentation will provide insights into the synthesis and biological evaluation of these small molecule inhibitors.

Discovery of novel series of LasR quorum sensing inhibitors in <i>Pseudomonas aeruginosa</i>

254th National Meeting (2017)

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Discovery of novel series of LasR quorum sensing inhibitors in Pseudomonas aeruginosa