Discovery of new Gram-negative antivirulence drugs: Structure and properties of novel E. coli WaaC inhibitors

Heptosyltransferases such as WaaC represent promising and attractive targets for the discovery of new Gram-negative antibacterial drugs based on antivirulence mechanisms. We report herein our approach to the identification of the first micromolar inhibitors of WaaC and the preliminary SAR generated from this family of 2-aryl-5-methyl-4-(5-aryl-furan-2-yl-methylene)-2,4-dihydro-pyrazol-3-ones identified by virtual screening.

Graphical abstractWaaC is a new Gram-negative antivirulence target. The identification by virtual screening of the first micromolar inhibitor 1a of this enzyme and the preliminary SAR generated from this family of aryl-pyrazolones is described.Figure optionsDownload full-size imageDownload as PowerPoint slide