Antagonism of a zinc metalloprotease using a unique metal-chelating scaffold: tropolones as inhibitors of P. aeruginosa elastaseElectronic supplementary information (ESI) available: Detailed synthesis, characterization, and assay procedures. See DOI: 10.1039/c3cc41191e

Tropolone emerged from the screening of a chelator fragment library (CFL) as an inhibitor of the Zn 2+ -dependent virulence factor, Pseudomonas aeruginosa elastase (LasB). Based on this initial hit, a series of substituted tropolone-based LasB inhibitors was prepared, and a compound displaying potent activity in vitro and in a bacterial swarming assay was identified. Importantly, this inhibitor was found to be specific for LasB over other metalloenzymes, validating the usage of tropolone as a viable scaffold for identifying first-in-class LasB inhibitors. Tropolone emerged from the screening of a chelator fragment library (CFL) as an inhibitor of the Zn 2+ -dependent virulence factor, Pseudomonas aeruginosa elastase (LasB).