2014•ACS Medicinal Chemistry LettersOpen access

Potent Irreversible Inhibitors of LasR Quorum Sensing in Pseudomonas aeruginosa

Kevin T. O’Brien, Joseph Noto, Luke Nichols-O’Neill, Lark J. Perez

Abstract

Antagonism of quorum sensing represents a promising new antivirulence approach for the treatment of bacterial infection. The development of a novel series of non-natural irreversible antagonists of P. aeruginosa LasR is described. The lead compounds identified (25 and 28) display potent LasR antagonist activity and inhibit expression of the P. aeruginosa virulence factors pyocyanin and biofilm formation in PAO1 and PA14.

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Key concepts: Quorum sensing, Pseudomonas aeruginosa, Microbiology, Chemistry, Bacteria, Biology, Biochemistry, Virulence