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Literature summary for 1.8.1.12 extracted from

  • De Gasparo, R.; Brodbeck-Persch, E.; Bryson, S.; Hentzen, N.B.; Kaiser, M.; Pai, E.F.; Krauth-Siegel, R.L.; Diederich, F.
    Biological evaluation and X-ray co-crystal structures of cyclohexylpyrrolidine ligands for trypanothione reductase, an enzyme from the redox metabolism of Trypanosoma (2018), ChemMedChem, 13, 957-967 .
    View publication on PubMed
Search for more literature for 1.8.1.12

Crystallization (Commentary)

Crystallization (Comment) Organism
hanging drop vapor diffusion method Trypanosoma brucei brucei

Inhibitors

Inhibitors Comment Organism Structure
1-ethyl-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 14% inhibition Trypanosoma brucei brucei
1-ethyl-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 27% inhibition Trypanosoma cruzi
1-[1-(4,5-diphenylthiophen-2-yl)cyclohexyl]pyrrolidine 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 11% inhibition Trypanosoma brucei brucei
1-[1-(4,5-diphenylthiophen-2-yl)cyclohexyl]pyrrolidine 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 15% inhibition Trypanosoma cruzi
1-[1-[4,5-bis(2H-1,3-benzodioxol-5-yl)thiophen-2-yl]cyclohexyl]pyrrolidine 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 11% inhibition Trypanosoma brucei brucei
1-[1-[4,5-bis(2H-1,3-benzodioxol-5-yl)thiophen-2-yl]cyclohexyl]pyrrolidine 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 23% inhibition Trypanosoma cruzi
1-[2-(4-methylpiperazin-1-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase,60 % inhibition Trypanosoma brucei brucei
1-[2-(4-methylpiperazin-1-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 78% inhibition Trypanosoma cruzi
1-[2-(morpholin-4-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 34% inhibition Trypanosoma brucei brucei
1-[2-(morpholin-4-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 38% inhibition Trypanosoma cruzi
1-[2-(piperazin-1-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 80% inhibition Trypanosoma brucei brucei
1-[2-(piperazin-1-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 88% inhibition Trypanosoma cruzi
1-[2-(piperidin-4-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 68% inhibition Trypanosoma brucei brucei
1-[2-(piperidin-4-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 84% inhibition Trypanosoma cruzi
3,3'-[5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophene-2,3-diyl]dipyridine 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 10% inhibition Trypanosoma brucei brucei
3,3'-[5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophene-2,3-diyl]dipyridine 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 10% inhibition Trypanosoma cruzi
5-[2-(1-benzothiophen-5-yl)-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-3-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 14% inhibition Trypanosoma brucei brucei
5-[2-(1-benzothiophen-5-yl)-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-3-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 41% inhibition Trypanosoma cruzi
5-[2-phenyl-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-3-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 29% inhibition Trypanosoma brucei brucei
5-[2-phenyl-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-3-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 38% inhibition Trypanosoma cruzi
5-[3-(1-benzothiophen-5-yl)-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 23% inhibition Trypanosoma brucei brucei
5-[3-(1-benzothiophen-5-yl)-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 43% inhibition Trypanosoma cruzi
5-[3-phenyl-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 14% inhibition Trypanosoma brucei brucei
5-[3-phenyl-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 41% inhibition Trypanosoma cruzi
5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 19% inhibition Trypanosoma brucei brucei
5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole 0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 51% inhibition Trypanosoma cruzi

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
trypanothione disulfide + NADPH + H+ Trypanosoma cruzi
-
 trypanothione + NADP+
-
 ?
trypanothione disulfide + NADPH + H+ Trypanosoma brucei brucei
-
 trypanothione + NADP+
-
 ?
trypanothione disulfide + NADPH + H+ Trypanosoma brucei brucei 927/4 GUTat10.1
-
 trypanothione + NADP+
-
 ?

Organism

Organism UniProt Comment Textmining
Trypanosoma brucei brucei Q389T8
-
-
Trypanosoma brucei brucei 927/4 GUTat10.1 Q389T8
-
-
Trypanosoma cruzi
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
trypanothione disulfide + NADPH + H+
-
 Trypanosoma cruzi trypanothione + NADP+
-
 ?
trypanothione disulfide + NADPH + H+
-
 Trypanosoma brucei brucei trypanothione + NADP+
-
 ?
trypanothione disulfide + NADPH + H+
-
 Trypanosoma brucei brucei 927/4 GUTat10.1 trypanothione + NADP+
-
 ?

Subunits

Subunits Comment Organism
homodimer
-
 Trypanosoma cruzi
homodimer
-
 Trypanosoma brucei brucei

Synonyms

Synonyms Comment Organism
trypanothione reductase
-
 Trypanosoma cruzi
trypanothione reductase
-
 Trypanosoma brucei brucei

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0021
-
 pH and temperature not specified in the publication Trypanosoma cruzi 1-[2-(piperazin-1-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole
0.0029
-
 pH and temperature not specified in the publication Trypanosoma cruzi 1-[2-(piperidin-4-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole
0.0032
-
 pH and temperature not specified in the publication Trypanosoma cruzi 1-[2-(4-methylpiperazin-1-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole
0.0038
-
 pH and temperature not specified in the publication Trypanosoma brucei brucei 1-[2-(piperazin-1-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole
0.004
-
 pH and temperature not specified in the publication Trypanosoma cruzi 5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole
0.0043
-
 pH and temperature not specified in the publication Trypanosoma cruzi 5-[2-phenyl-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-3-yl]-1H-indole
0.0048
-
 pH and temperature not specified in the publication Trypanosoma cruzi 5-[3-(1-benzothiophen-5-yl)-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole
0.0056
-
 pH and temperature not specified in the publication Trypanosoma cruzi 5-[3-phenyl-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole
0.0063
-
 pH and temperature not specified in the publication Trypanosoma cruzi 5-[2-(1-benzothiophen-5-yl)-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-3-yl]-1H-indole
0.0065
-
 pH and temperature not specified in the publication Trypanosoma brucei brucei 1-[2-(4-methylpiperazin-1-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole
0.01
-
 pH and temperature not specified in the publication Trypanosoma brucei brucei 5-[2-phenyl-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-3-yl]-1H-indole
0.012
-
 pH and temperature not specified in the publication Trypanosoma brucei brucei 5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole
0.02
-
 pH and temperature not specified in the publication Trypanosoma brucei brucei 5-[3-(1-benzothiophen-5-yl)-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole
0.025
-
 pH and temperature not specified in the publication Trypanosoma brucei brucei 5-[3-phenyl-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole
0.035
-
 pH and temperature not specified in the publication Trypanosoma brucei brucei 5-[2-(1-benzothiophen-5-yl)-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-3-yl]-1H-indole

General Information

General Information Comment Organism
drug target the enzyme is a promising targets for the development of drugs selective against parasites of the family of trypanosomatids Trypanosoma cruzi
drug target the enzyme is a promising targets for the development of drugs selective against parasites of the family of trypanosomatids Trypanosoma brucei brucei
physiological function trypanosomatids possess a unique redox metabolism based on the dithiol trypanothione and the enzyme trypanothione reductase (TR) that differs distinctively from the glutathione and glutathione reductase-based metabolism in mammals Trypanosoma cruzi
physiological function trypanosomatids possess a unique redox metabolism based on the dithiol trypanothione and the enzyme trypanothione reductase (TR) that differs distinctively from the glutathione and glutathione reductase-based metabolism in mammals Trypanosoma brucei brucei