Issue 31, 2013

Antagonism of a zinc metalloprotease using a unique metal-chelating scaffold: tropolones as inhibitors of P. aeruginosa elastase

Abstract

Tropolone emerged from the screening of a chelator fragment library (CFL) as an inhibitor of the Zn2+-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.

Graphical abstract: Antagonism of a zinc metalloprotease using a unique metal-chelating scaffold: tropolones as inhibitors of P. aeruginosa elastase

Supplementary files

Article information

Article type
Communication
Submitted
13 2 2013
Accepted
05 3 2013
First published
06 3 2013

Chem. Commun., 2013,49, 3197-3199

Antagonism of a zinc metalloprotease using a unique metal-chelating scaffold: tropolones as inhibitors of P. aeruginosa elastase

J. L. Fullagar, A. L. Garner, A. K. Struss, J. A. Day, D. P. Martin, J. Yu, X. Cai, K. D. Janda and S. M. Cohen, Chem. Commun., 2013, 49, 3197 DOI: 10.1039/C3CC41191E

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