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 (Comment) | Organism |
---|---|
recombinant expression of His-tagged enzyme in Escherichia coli strain BL21 Codon PLUS-RIL | Mycobacterium tuberculosis |
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 | UniProt | Comment | Textmining |
---|---|---|---|
Mycobacterium tuberculosis | P9WN39 | - |
- |
Mycobacterium tuberculosis ATCC 25618 / H37Rv | P9WN39 | - |
- |
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 | Comment | Organism |
---|---|---|
? | x * 54000, SDS-PAGE | Mycobacterium tuberculosis |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
22 | - |
assay at room temperature | Mycobacterium tuberculosis |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.5 | - |
assay at | Mycobacterium tuberculosis |
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) |