Novel HldE-K inhibitors leading to attenuated Gram negative bacterial virulence

…, A Denis, C Oliveira, D Atamanyuk, S Briet…

Index: Desroy, Nicolas; Denis, Alexis; Oliveira, Chrystelle; Atamanyuk, Dmytro; Briet, Sophia; Faivre, Fabien; Lefralliec, Geraldine; Bonvin, Yannick; Oxoby, Mayalen; Escaich, Sonia; Floquet, Stephanie; Drocourt, Elodie; Vongsouthi, Vanida; Durant, Lionel; Moreau, Francois; Verhey, Theodore B.; Lee, Ting-Wai; Junop, Murray S.; Gerusz, Vincent Journal of Medicinal Chemistry, 2013 , vol. 56, # 4 p. 1418 - 1430

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Citation Number: 10

Abstract

We report here the optimization of an HldE kinase inhibitor to low nanomolar potency, which resulted in the identification of the first reported compounds active on selected E. coli strains. One of the most interesting candidates, compound 86, was shown to inhibit specifically bacterial LPS heptosylation on efflux pump deleted E. coli strains. This compound did not interfere with E. coli bacterial growth (MIC> 32 μg/mL) but sensitized this pathogen to ...