BRENDA - Enzyme Database

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

Moreau, F.; Desroy, N.; Genevard, J.M.; Vongsouthi, V.; Gerusz, V.; Le Fralliec, G.; Oliveira, C.; Floquet, S.; Denis, A.; Escaich, S.; Wolf, K.; Busemann, M.; Aschenbrenner, A.; Bioorg. Med. Chem. Lett. 18, 4022-4026 (2008)

Data extracted from this reference:

Application
EC Number
Application
Commentary
Organism
2.4.99.B6
medicine
the enzyme represent a promising and attractive target for the discovery of new Gram-negative antibacterial drugs based on antivirulence mechanisms
Escherichia coli
Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
2.4.99.B6
2-aryl-5-methyl-4-(5-aryl-furan-2-yl-methylene)-2,4-dihydro-pyrazol-3-one
micromolar inhibitors are identified by virtual screening, promising lead series for further optimization as antivirulence drug
Escherichia coli
2.4.99.B6
3-[(4Z)-4-([5-[3-(methoxycarbonyl)phenyl]furan-2-yl]methylidene)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
Escherichia coli
2.4.99.B6
3-[(4Z)-4-[[5-(3-acetylphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
Escherichia coli
2.4.99.B6
3-[(4Z)-4-[[5-(3-carboxyphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
Escherichia coli
2.4.99.B6
3-[(4Z)-4-[[5-(4-carboxyphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
Escherichia coli
2.4.99.B6
4-(5-[(Z)-[1-(3-carboxyphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)-2-methylbenzoic acid
-
Escherichia coli
2.4.99.B6
4-[(4Z)-3-methyl-5-oxo-4-[(5-phenylfuran-2-yl)methylidene]-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
Escherichia coli
2.4.99.B6
4-[(4Z)-4-[[5-(3-carbamoylphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
Escherichia coli
2.4.99.B6
4-[(4Z)-4-[[5-(4-carboxyphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
Escherichia coli
2.4.99.B6
5-(5-[(Z)-[1-(3-carboxyphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)-2-chlorobenzoic acid
-
Escherichia coli
2.4.99.B6
5-(5-[(Z)-[1-(4-carboxyphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)-2-chlorobenzoic acid
-
Escherichia coli
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
2.4.99.B6
Escherichia coli
P24173
-
-
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2.4.99.B6
ADP-L-glycero-beta-D-manno-heptose + lipopolysaccahride from Salmonella minnesota R595
-
727135
Escherichia coli
ADP + ?
-
-
-
?
Ki Value [mM]
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
2.4.99.B6
0.001
-
5-(5-[(Z)-[1-(3-carboxyphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)-2-chlorobenzoic acid
pH and temperature not specified in the publication
Escherichia coli
2.4.99.B6
0.002
-
3-[(4Z)-4-[[5-(3-carboxyphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
pH and temperature not specified in the publication
Escherichia coli
2.4.99.B6
0.003
-
3-[(4Z)-4-[[5-(4-carboxyphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
pH and temperature not specified in the publication
Escherichia coli
2.4.99.B6
0.0031
-
5-(5-[(Z)-[1-(4-carboxyphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)-2-chlorobenzoic acid
pH and temperature not specified in the publication
Escherichia coli
2.4.99.B6
0.015
-
3-[(4Z)-4-[[5-(3-acetylphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
pH and temperature not specified in the publication
Escherichia coli
2.4.99.B6
0.018
-
4-[(4Z)-4-[[5-(3-carbamoylphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
pH and temperature not specified in the publication
Escherichia coli
2.4.99.B6
0.031
-
4-(5-[(Z)-[1-(3-carboxyphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)-2-methylbenzoic acid
pH and temperature not specified in the publication
Escherichia coli
2.4.99.B6
0.049
-
3-[(4Z)-4-([5-[3-(methoxycarbonyl)phenyl]furan-2-yl]methylidene)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
pH and temperature not specified in the publication
Escherichia coli
2.4.99.B6
0.051
-
4-[(4Z)-4-[[5-(4-carboxyphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
pH and temperature not specified in the publication
Escherichia coli
2.4.99.B6
0.055
-
4-[(4Z)-3-methyl-5-oxo-4-[(5-phenylfuran-2-yl)methylidene]-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
pH and temperature not specified in the publication
Escherichia coli
Application (protein specific)
EC Number
Application
Commentary
Organism
2.4.99.B6
medicine
the enzyme represent a promising and attractive target for the discovery of new Gram-negative antibacterial drugs based on antivirulence mechanisms
Escherichia coli
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
2.4.99.B6
2-aryl-5-methyl-4-(5-aryl-furan-2-yl-methylene)-2,4-dihydro-pyrazol-3-one
micromolar inhibitors are identified by virtual screening, promising lead series for further optimization as antivirulence drug
Escherichia coli
2.4.99.B6
3-[(4Z)-4-([5-[3-(methoxycarbonyl)phenyl]furan-2-yl]methylidene)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
Escherichia coli
2.4.99.B6
3-[(4Z)-4-[[5-(3-acetylphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
Escherichia coli
2.4.99.B6
3-[(4Z)-4-[[5-(3-carboxyphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
Escherichia coli
2.4.99.B6
3-[(4Z)-4-[[5-(4-carboxyphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
Escherichia coli
2.4.99.B6
4-(5-[(Z)-[1-(3-carboxyphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)-2-methylbenzoic acid
-
Escherichia coli
2.4.99.B6
4-[(4Z)-3-methyl-5-oxo-4-[(5-phenylfuran-2-yl)methylidene]-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
Escherichia coli
2.4.99.B6
4-[(4Z)-4-[[5-(3-carbamoylphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
Escherichia coli
2.4.99.B6
4-[(4Z)-4-[[5-(4-carboxyphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
Escherichia coli
2.4.99.B6
5-(5-[(Z)-[1-(3-carboxyphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)-2-chlorobenzoic acid
-
Escherichia coli
2.4.99.B6
5-(5-[(Z)-[1-(4-carboxyphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)-2-chlorobenzoic acid
-
Escherichia coli
Ki Value [mM] (protein specific)
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
2.4.99.B6
0.001
-
5-(5-[(Z)-[1-(3-carboxyphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)-2-chlorobenzoic acid
pH and temperature not specified in the publication
Escherichia coli
2.4.99.B6
0.002
-
3-[(4Z)-4-[[5-(3-carboxyphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
pH and temperature not specified in the publication
Escherichia coli
2.4.99.B6
0.003
-
3-[(4Z)-4-[[5-(4-carboxyphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
pH and temperature not specified in the publication
Escherichia coli
2.4.99.B6
0.0031
-
5-(5-[(Z)-[1-(4-carboxyphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)-2-chlorobenzoic acid
pH and temperature not specified in the publication
Escherichia coli
2.4.99.B6
0.015
-
3-[(4Z)-4-[[5-(3-acetylphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
pH and temperature not specified in the publication
Escherichia coli
2.4.99.B6
0.018
-
4-[(4Z)-4-[[5-(3-carbamoylphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
pH and temperature not specified in the publication
Escherichia coli
2.4.99.B6
0.031
-
4-(5-[(Z)-[1-(3-carboxyphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)-2-methylbenzoic acid
pH and temperature not specified in the publication
Escherichia coli
2.4.99.B6
0.049
-
3-[(4Z)-4-([5-[3-(methoxycarbonyl)phenyl]furan-2-yl]methylidene)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
pH and temperature not specified in the publication
Escherichia coli
2.4.99.B6
0.051
-
4-[(4Z)-4-[[5-(4-carboxyphenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
pH and temperature not specified in the publication
Escherichia coli
2.4.99.B6
0.055
-
4-[(4Z)-3-methyl-5-oxo-4-[(5-phenylfuran-2-yl)methylidene]-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
pH and temperature not specified in the publication
Escherichia coli
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2.4.99.B6
ADP-L-glycero-beta-D-manno-heptose + lipopolysaccahride from Salmonella minnesota R595
-
727135
Escherichia coli
ADP + ?
-
-
-
?