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.
Moreau
F
F
MUTABILIS SA, 102 Avenue Gaston Roussel, 93230 Romainville, France.
Desroy
N
N
Genevard
J M
JM
Vongsouthi
V
V
Gerusz
V
V
Le Fralliec
G
G
Oliveira
C
C
Floquet
S
S
Denis
A
A
Escaich
S
S
Wolf
K
K
Busemann
M
M
Aschenbrenner
A
A
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology; D001665:Binding Sites; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018360:Crystallography, X-Ray / Q000379:methods; D015195:Drug Design; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D016695:Glycosyltransferases / Q000378:metabolism*; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D016695:Glycosyltransferases; C080934:lipooligosaccharide 1,5-heptosyltransferase