Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary 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

EC Number Application Comment Organism
6.3.1.2 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)

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

Inhibitors

EC Number Inhibitors Comment Organism Structure
6.3.1.2 ([[(2,4-dichlorophenyl)methyl]amino]methylene)bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 ([[(2,5-dichlorophenyl)methyl]amino]methylene)bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 3,4-dichlorophenylethylidene-1-hydroxy-1,1-bisphosphonic acid
-
Mycobacterium tuberculosis
6.3.1.2 3,5-difluorophenylaminoethylidenebisphosphonic acid
-
Mycobacterium tuberculosis
6.3.1.2 4-methylphenylethylidene-1-hydroxy-1,1-bisphosphonic acid
-
Mycobacterium tuberculosis
6.3.1.2 4-[2-tert-butyl-4-(6-methoxynaphthalen-2-yl)-1H-imidazol-5-yl]pyridin-2-amine
-
Mycobacterium tuberculosis
6.3.1.2 benzylethylidene-1-hydroxy-1,1-bisphosphonic acid
-
Mycobacterium tuberculosis
6.3.1.2 L-methionine-S-sulfoximine
-
Mycobacterium tuberculosis
6.3.1.2 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
6.3.1.2 N-(4-isopropylphenyl)aminomethylenebisphosphonic acid
-
Mycobacterium tuberculosis
6.3.1.2 N-(4-methylphenyl)aminoethalidenebisphosphonic acid
-
Mycobacterium tuberculosis
6.3.1.2 N-phenylaminoethalidenebisphosphonic acid
-
Mycobacterium tuberculosis
6.3.1.2 N-phenylaminomethylenebisphosphonic acid
-
Mycobacterium tuberculosis
6.3.1.2 phenylethylidene-1-hydroxy-1,1-bisphosphonic acid
-
Mycobacterium tuberculosis
6.3.1.2 phenylmethylidene-1-hydroxy-1,1-bisphosphonic acid
-
Mycobacterium tuberculosis
6.3.1.2 Phosphinothricin
-
Mycobacterium tuberculosis
6.3.1.2 [(2-chloro-3-methylphenyl)(hydroxy)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [(2-chloroanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [(3,4-dichloroanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [(3,5-dichloroanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [(3,5-difluoroanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [(3,5-dimethylanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [(3,5-dimethylphenyl)(hydroxy)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [(3-carbamoylanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [(3-chloroanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [(4-benzylanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [(4-benzylphenyl)(hydroxy)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [(4-chloroanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [(4-methylanilino)methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [2-(2,3-dichlorophenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [2-(2,6-dichloroanilino)ethane-1,1-diyl]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [2-(2,6-dichlorophenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [2-(3,5-dichloroanilino)ethane-1,1-diyl]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [2-(3,5-dimethylphenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [2-(4-benzylanilino)ethane-1,1-diyl]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [2-(4-chlorophenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [2-[(5,6,7,8-tetrahydronaphthalen-1-yl)amino]ethane-1,1-diyl]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [2-[3,5-bis(trifluoromethyl)anilino]ethane-1,1-diyl]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [[(2,3-dihydro-1H-inden-5-yl)amino]methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [[(5,6,7,8-tetrahydronaphthalen-2-yl)amino]methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis
6.3.1.2 [[3-(trifluoromethyl)anilino]methylene]bis(phosphonic acid)
-
Mycobacterium tuberculosis

Organism

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

Purification (Commentary)

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

Subunits

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

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
6.3.1.2 22
-
assay at room temperature Mycobacterium tuberculosis

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
6.3.1.2 7.5
-
assay at Mycobacterium tuberculosis

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
6.3.1.2 0.053
-
pH 7.5, 22°C Mycobacterium tuberculosis 3,4-dichlorophenylethylidene-1-hydroxy-1,1-bisphosphonic acid
6.3.1.2 0.082
-
pH 7.5, 22°C Mycobacterium tuberculosis 3,5-difluorophenylaminoethylidenebisphosphonic acid
6.3.1.2 0.082
-
pH 7.5, 22°C Mycobacterium tuberculosis [2-(3,5-dichloroanilino)ethane-1,1-diyl]bis(phosphonic acid)
6.3.1.2 0.104
-
pH 7.5, 22°C, recombinant enzyme Mycobacterium tuberculosis L-methionine-S-sulfoximine
6.3.1.2 0.125
-
pH 7.5, 22°C Mycobacterium tuberculosis 4-methylphenylethylidene-1-hydroxy-1,1-bisphosphonic acid
6.3.1.2 0.13
-
pH 7.5, 22°C Mycobacterium tuberculosis [2-(4-chlorophenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
6.3.1.2 0.168
-
pH 7.5, 22°C Mycobacterium tuberculosis [2-[3,5-bis(trifluoromethyl)anilino]ethane-1,1-diyl]bis(phosphonic acid)
6.3.1.2 0.174
-
pH 7.5, 22°C Mycobacterium tuberculosis N-phenylaminoethalidenebisphosphonic acid
6.3.1.2 0.178
-
pH 7.5, 22°C Mycobacterium tuberculosis [2-(2,3-dichlorophenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
6.3.1.2 0.18
-
pH 7.5, 22°C Mycobacterium tuberculosis [2-(2,6-dichloroanilino)ethane-1,1-diyl]bis(phosphonic acid)
6.3.1.2 0.186
-
pH 7.5, 22°C Mycobacterium tuberculosis [(2-chloro-3-methylphenyl)(hydroxy)methylene]bis(phosphonic acid)
6.3.1.2 0.194
-
pH 7.5, 22°C Mycobacterium tuberculosis [2-(2,6-dichlorophenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
6.3.1.2 0.221
-
pH 7.5, 22°C Mycobacterium tuberculosis phenylethylidene-1-hydroxy-1,1-bisphosphonic acid
6.3.1.2 0.227
-
pH 7.5, 22°C Mycobacterium tuberculosis [(3,5-dimethylanilino)methylene]bis(phosphonic acid)
6.3.1.2 0.228
-
pH 7.5, 22°C Mycobacterium tuberculosis [(3,5-dichloroanilino)methylene]bis(phosphonic acid)
6.3.1.2 0.231
-
pH 7.5, 22°C Mycobacterium tuberculosis N-(4-isopropylphenyl)aminomethylenebisphosphonic acid
6.3.1.2 0.24
-
pH 7.5, 22°C Mycobacterium tuberculosis [(3-chloroanilino)methylene]bis(phosphonic acid)
6.3.1.2 0.244
-
pH 7.5, 22°C Mycobacterium tuberculosis benzylethylidene-1-hydroxy-1,1-bisphosphonic acid
6.3.1.2 0.246
-
pH 7.5, 22°C Mycobacterium tuberculosis N-phenylaminomethylenebisphosphonic acid
6.3.1.2 0.249
-
pH 7.5, 22°C Mycobacterium tuberculosis N-(4-methylphenyl)aminoethalidenebisphosphonic acid
6.3.1.2 0.25
-
pH 7.5, 22°C Mycobacterium tuberculosis [(4-benzylanilino)methylene]bis(phosphonic acid)
6.3.1.2 0.256
-
pH 7.5, 22°C Mycobacterium tuberculosis [[3-(trifluoromethyl)anilino]methylene]bis(phosphonic acid)
6.3.1.2 0.269
-
pH 7.5, 22°C Mycobacterium tuberculosis [(3,5-difluoroanilino)methylene]bis(phosphonic acid)
6.3.1.2 0.273
-
pH 7.5, 22°C Mycobacterium tuberculosis [(3-carbamoylanilino)methylene]bis(phosphonic acid)
6.3.1.2 0.278
-
pH 7.5, 22°C Mycobacterium tuberculosis [[(5,6,7,8-tetrahydronaphthalen-2-yl)amino]methylene]bis(phosphonic acid)
6.3.1.2 0.286
-
pH 7.5, 22°C Mycobacterium tuberculosis [2-(4-benzylanilino)ethane-1,1-diyl]bis(phosphonic acid)
6.3.1.2 0.286
-
pH 7.5, 22°C Mycobacterium tuberculosis [[(2,3-dihydro-1H-inden-5-yl)amino]methylene]bis(phosphonic acid)
6.3.1.2 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)
6.3.1.2 0.317
-
pH 7.5, 22°C Mycobacterium tuberculosis [(3,4-dichloroanilino)methylene]bis(phosphonic acid)
6.3.1.2 0.331
-
pH 7.5, 22°C Mycobacterium tuberculosis ([[(2,5-dichlorophenyl)methyl]amino]methylene)bis(phosphonic acid)
6.3.1.2 0.345
-
pH 7.5, 22°C Mycobacterium tuberculosis [(3,5-dimethylphenyl)(hydroxy)methylene]bis(phosphonic acid)
6.3.1.2 0.348
-
pH 7.5, 22°C Mycobacterium tuberculosis phenylmethylidene-1-hydroxy-1,1-bisphosphonic acid
6.3.1.2 0.358
-
pH 7.5, 22°C Mycobacterium tuberculosis [(2-chloroanilino)methylene]bis(phosphonic acid)
6.3.1.2 0.363
-
pH 7.5, 22°C Mycobacterium tuberculosis [(4-benzylphenyl)(hydroxy)methylene]bis(phosphonic acid)
6.3.1.2 0.375
-
pH 7.5, 22°C Mycobacterium tuberculosis [(4-chloroanilino)methylene]bis(phosphonic acid)
6.3.1.2 0.447
-
pH 7.5, 22°C Mycobacterium tuberculosis ([[(2,4-dichlorophenyl)methyl]amino]methylene)bis(phosphonic acid)
6.3.1.2 0.45
-
pH 7.5, 22°C Mycobacterium tuberculosis [2-(3,5-dimethylphenyl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
6.3.1.2 0.525
-
pH 7.5, 22°C Mycobacterium tuberculosis [(4-methylanilino)methylene]bis(phosphonic acid)