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Literature summary for 6.3.1.2 extracted from

  • Kosikowska, P.; Bochno, M.; Macegoniuk, K.; Forlani, G.; Kafarski, P.; Berlicki, L.
    Bisphosphonic acids as effective inhibitors of Mycobacterium tuberculosis glutamine synthetase (2016), J. Enzyme Inhib. Med. Chem., 31, 931-938 .
    View publication on PubMed

Application

Application Comment Organism
drug development inhibition of glutamine synthetase is one of the most promising strategies for the discovery of drugs against tuberculosis. The bone-targeting properties of the bisphosphonate compounds make them attractive agents for the treatment of bone tuberculosis Mycobacterium tuberculosis

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of His-tagged enzyme in Escherichia coli strain BL21 Codon PLUS-RIL Mycobacterium tuberculosis

Inhibitors

Inhibitors Comment Organism Structure
([[(2,4-dichlorophenyl)methyl]amino]methylene)bis(phosphonic acid)
-
Mycobacterium tuberculosis
([[(2,5-dichlorophenyl)methyl]amino]methylene)bis(phosphonic acid)
-
Mycobacterium tuberculosis
3,4-dichlorophenylethylidene-1-hydroxy-1,1-bisphosphonic acid
-
Mycobacterium tuberculosis
3,5-difluorophenylaminoethylidenebisphosphonic acid
-
Mycobacterium tuberculosis
4-methylphenylethylidene-1-hydroxy-1,1-bisphosphonic acid
-
Mycobacterium tuberculosis
4-[2-tert-butyl-4-(6-methoxynaphthalen-2-yl)-1H-imidazol-5-yl]pyridin-2-amine
-
Mycobacterium tuberculosis
benzylethylidene-1-hydroxy-1,1-bisphosphonic acid
-
Mycobacterium tuberculosis
L-methionine-S-sulfoximine
-
Mycobacterium tuberculosis
additional information 43 bisphosphonic and bis-H-phosphinic acids of various scaffolds, bearing aromatic substituents, are synthesized and screened against recombinant enzyme from Mycobacterium tuberculosis. Some of the inhibitors are much more effective against the pathogen enzyme than against the human orthologue. Bone-targeting properties of the bisphosphonate compounds. No inhibition by [(3,5-dibromoanilino)methylene]bis(phosphonic acid), [[3,5-bis(trifluoromethyl)anilino]methylene]bis(phosphonic acid), (anilinomethylene)di(lambda5-phosphanedione), [(4-methylanilino)methylene]di(lambda5-phosphanedione), [(3,5-dichloroanilino)methylene]di(lambda5-phosphanedione), and [(4-benzylanilino)methylene]di(lambda5-phosphanedione). Molecular modeling Mycobacterium tuberculosis
N-(4-isopropylphenyl)aminomethylenebisphosphonic acid
-
Mycobacterium tuberculosis
N-(4-methylphenyl)aminoethalidenebisphosphonic acid
-
Mycobacterium tuberculosis
N-phenylaminoethalidenebisphosphonic acid
-
Mycobacterium tuberculosis
N-phenylaminomethylenebisphosphonic acid
-
Mycobacterium tuberculosis
phenylethylidene-1-hydroxy-1,1-bisphosphonic acid
-
Mycobacterium tuberculosis
phenylmethylidene-1-hydroxy-1,1-bisphosphonic acid
-
Mycobacterium tuberculosis
Phosphinothricin
-
Mycobacterium tuberculosis
[(2-chloro-3-methylphenyl)(hydroxy)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[(2-chloroanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[(3,4-dichloroanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[(3,5-dichloroanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[(3,5-difluoroanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[(3,5-dimethylanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[(3,5-dimethylphenyl)(hydroxy)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[(3-carbamoylanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[(3-chloroanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[(4-benzylanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[(4-benzylphenyl)(hydroxy)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[(4-chloroanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[(4-methylanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[2-(2,3-dichlorophenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[2-(2,6-dichloroanilino)ethane-1,1-diyl]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[2-(2,6-dichlorophenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[2-(3,5-dichloroanilino)ethane-1,1-diyl]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[2-(3,5-dimethylphenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[2-(4-benzylanilino)ethane-1,1-diyl]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[2-(4-chlorophenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[2-[(5,6,7,8-tetrahydronaphthalen-1-yl)amino]ethane-1,1-diyl]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[2-[3,5-bis(trifluoromethyl)anilino]ethane-1,1-diyl]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[[(2,3-dihydro-1H-inden-5-yl)amino]methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[[(5,6,7,8-tetrahydronaphthalen-2-yl)amino]methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
[[3-(trifluoromethyl)anilino]methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis P9WN39
-
-
Mycobacterium tuberculosis ATCC 25618 / H37Rv P9WN39
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His-tagged enzyme from Escherichia coli strain BL21 Codon PLUS-RIL by nickel affinity chromatography and gel filtration Mycobacterium tuberculosis

Subunits

Subunits Comment Organism
? x * 54000, SDS-PAGE Mycobacterium tuberculosis

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
22
-
assay at room temperature Mycobacterium tuberculosis

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Mycobacterium tuberculosis

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.053
-
pH 7.5, 22°C Mycobacterium tuberculosis 3,4-dichlorophenylethylidene-1-hydroxy-1,1-bisphosphonic acid
0.082
-
pH 7.5, 22°C Mycobacterium tuberculosis 3,5-difluorophenylaminoethylidenebisphosphonic acid
0.082
-
pH 7.5, 22°C Mycobacterium tuberculosis [2-(3,5-dichloroanilino)ethane-1,1-diyl]bis(phosphonic acid)
0.104
-
pH 7.5, 22°C, recombinant enzyme Mycobacterium tuberculosis L-methionine-S-sulfoximine
0.125
-
pH 7.5, 22°C Mycobacterium tuberculosis 4-methylphenylethylidene-1-hydroxy-1,1-bisphosphonic acid
0.13
-
pH 7.5, 22°C Mycobacterium tuberculosis [2-(4-chlorophenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
0.168
-
pH 7.5, 22°C Mycobacterium tuberculosis [2-[3,5-bis(trifluoromethyl)anilino]ethane-1,1-diyl]bis(phosphonic acid)
0.174
-
pH 7.5, 22°C Mycobacterium tuberculosis N-phenylaminoethalidenebisphosphonic acid
0.178
-
pH 7.5, 22°C Mycobacterium tuberculosis [2-(2,3-dichlorophenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
0.18
-
pH 7.5, 22°C Mycobacterium tuberculosis [2-(2,6-dichloroanilino)ethane-1,1-diyl]bis(phosphonic acid)
0.186
-
pH 7.5, 22°C Mycobacterium tuberculosis [(2-chloro-3-methylphenyl)(hydroxy)methylene]bis(phosphonic acid)
0.194
-
pH 7.5, 22°C Mycobacterium tuberculosis [2-(2,6-dichlorophenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
0.221
-
pH 7.5, 22°C Mycobacterium tuberculosis phenylethylidene-1-hydroxy-1,1-bisphosphonic acid
0.227
-
pH 7.5, 22°C Mycobacterium tuberculosis [(3,5-dimethylanilino)methylene]bis(phosphonic acid)
0.228
-
pH 7.5, 22°C Mycobacterium tuberculosis [(3,5-dichloroanilino)methylene]bis(phosphonic acid)
0.231
-
pH 7.5, 22°C Mycobacterium tuberculosis N-(4-isopropylphenyl)aminomethylenebisphosphonic acid
0.24
-
pH 7.5, 22°C Mycobacterium tuberculosis [(3-chloroanilino)methylene]bis(phosphonic acid)
0.244
-
pH 7.5, 22°C Mycobacterium tuberculosis benzylethylidene-1-hydroxy-1,1-bisphosphonic acid
0.246
-
pH 7.5, 22°C Mycobacterium tuberculosis N-phenylaminomethylenebisphosphonic acid
0.249
-
pH 7.5, 22°C Mycobacterium tuberculosis N-(4-methylphenyl)aminoethalidenebisphosphonic acid
0.25
-
pH 7.5, 22°C Mycobacterium tuberculosis [(4-benzylanilino)methylene]bis(phosphonic acid)
0.256
-
pH 7.5, 22°C Mycobacterium tuberculosis [[3-(trifluoromethyl)anilino]methylene]bis(phosphonic acid)
0.269
-
pH 7.5, 22°C Mycobacterium tuberculosis [(3,5-difluoroanilino)methylene]bis(phosphonic acid)
0.273
-
pH 7.5, 22°C Mycobacterium tuberculosis [(3-carbamoylanilino)methylene]bis(phosphonic acid)
0.278
-
pH 7.5, 22°C Mycobacterium tuberculosis [[(5,6,7,8-tetrahydronaphthalen-2-yl)amino]methylene]bis(phosphonic acid)
0.286
-
pH 7.5, 22°C Mycobacterium tuberculosis [2-(4-benzylanilino)ethane-1,1-diyl]bis(phosphonic acid)
0.286
-
pH 7.5, 22°C Mycobacterium tuberculosis [[(2,3-dihydro-1H-inden-5-yl)amino]methylene]bis(phosphonic acid)
0.294
-
pH 7.5, 22°C Mycobacterium tuberculosis [2-[(5,6,7,8-tetrahydronaphthalen-1-yl)amino]ethane-1,1-diyl]bis(phosphonic acid)
0.317
-
pH 7.5, 22°C Mycobacterium tuberculosis [(3,4-dichloroanilino)methylene]bis(phosphonic acid)
0.331
-
pH 7.5, 22°C Mycobacterium tuberculosis ([[(2,5-dichlorophenyl)methyl]amino]methylene)bis(phosphonic acid)
0.345
-
pH 7.5, 22°C Mycobacterium tuberculosis [(3,5-dimethylphenyl)(hydroxy)methylene]bis(phosphonic acid)
0.348
-
pH 7.5, 22°C Mycobacterium tuberculosis phenylmethylidene-1-hydroxy-1,1-bisphosphonic acid
0.358
-
pH 7.5, 22°C Mycobacterium tuberculosis [(2-chloroanilino)methylene]bis(phosphonic acid)
0.363
-
pH 7.5, 22°C Mycobacterium tuberculosis [(4-benzylphenyl)(hydroxy)methylene]bis(phosphonic acid)
0.375
-
pH 7.5, 22°C Mycobacterium tuberculosis [(4-chloroanilino)methylene]bis(phosphonic acid)
0.447
-
pH 7.5, 22°C Mycobacterium tuberculosis ([[(2,4-dichlorophenyl)methyl]amino]methylene)bis(phosphonic acid)
0.45
-
pH 7.5, 22°C Mycobacterium tuberculosis [2-(3,5-dimethylphenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
0.525
-
pH 7.5, 22°C Mycobacterium tuberculosis [(4-methylanilino)methylene]bis(phosphonic acid)