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Literature summary for 1.8.1.12 extracted from

  • Holloway, G.A.; Baell, J.B.; Fairlamb, A.H.; Novello, P.M.; Parisot, J.P.; Richardson, J.; Watson, K.G.; Street, I.P.
    Discovery of 2-iminobenzimidazoles as a new class of trypanothione reductase inhibitor by high-throughput screening (2006), Bioorg. Med. Chem. Lett., 17, 1422-1427.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
pharmacology trypanothione reductase plays a central role in the trypanosomatid parasite’s defense against oxidative stress, trypanothione reductase is a promising target for antitrypanosomal drugs, 2-iminobenzimidazole class are potent trypanothione reductase inhibitors against Trypanosoma brucei rhodesiense and low cytotoxicity against human cells Trypanosoma brucei rhodesiense

Inhibitors

Inhibitors Comment Organism Structure
1,1'-[ethane-1,2-diylbis(oxyethane-2,1-diyl)]bis(3-benzyl-1,3-dihydro-2H-benzimidazol-2-imine)
-
Trypanosoma brucei rhodesiense
1,1'-[methanediylbis(oxyethane-2,1-diyl)]bis(3-methyl-1,3-dihydro-2H-benzimidazol-2-imine) IC50: 0.1 mM Trypanosoma brucei
1,1'-[methanediylbis(oxyethane-2,1-diyl)]bis(3-phenyl-1,3-dihydro-2H-benzimidazol-2-imine) IC50: 0.004 mM Trypanosoma brucei
1-(1-methylpiperidin-3-yl)-3-(2-phenoxyethyl)-1,3-dihydro-2H-benzimidazol-2-imine IC50: 0.1 mM Trypanosoma brucei
1-(2,4-dichlorophenoxy)-3-[2-imino-3-(2-piperidin-1-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]propan-2-ol IC50: 0.005 mM Trypanosoma brucei
1-(2-phenoxyethyl)-3-(2-piperidin-1-ylethyl)-1,3-dihydro-2H-benzimidazol-2-imine IC50: 0.004 mM Trypanosoma brucei
1-(3,4-dichlorophenyl)-2-[2-imino-3-(2-piperidin-1-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]ethanol IC50: 0.004 mM Trypanosoma brucei
1-(3,4-dichlorophenyl)-2-[2-imino-3-(2-piperidin-1-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]ethanol
-
Trypanosoma brucei rhodesiense
1-(3,4-dichlorophenyl)-2-[3-[2-(diethylamino)ethyl]-2-imino-2,3-dihydro-1H-benzimidazol-1-yl]ethanol IC50: 0.009 mM Trypanosoma brucei
1-(3,4-dichlorophenyl)-2-[3-[2-(diethylamino)ethyl]-2-imino-2,3-dihydro-1H-benzimidazol-1-yl]ethanone IC50: 0.01 mM Trypanosoma brucei
1-(3,4-dichlorophenyl)-2-[3-[2-(dimethylamino)ethyl]-2-imino-2,3-dihydro-1H-benzimidazol-1-yl]ethanol IC50: 0.01 mM, 92% inhibition at 0.025 mM Trypanosoma brucei
1-(3,4-dichlorophenyl)-2-[3-[2-(dimethylamino)ethyl]-2-imino-2,3-dihydro-1H-benzimidazol-1-yl]ethanol
-
Trypanosoma brucei rhodesiense
1-(3-phenoxypropyl)-3-(2-piperidin-1-ylethyl)-1,3-dihydro-2H-benzimidazol-2-imine IC50: 0.007 mM Trypanosoma brucei
1-(4-bromophenyl)-2-(3-butyl-2-imino-2,3-dihydro-1H-benzimidazol-1-yl)ethanol IC50: 0.1 mM, 42% inhibition at 0.025 mM Trypanosoma brucei
1-(4-ethoxyphenyl)-2-(2-imino-3-prop-2-en-1-yl-2,3-dihydro-1H-benzimidazol-1-yl)ethanol IC50: 0.1 mM, 6% inhibition at 0.025 mM Trypanosoma brucei
1-(5-phenoxypentyl)-3-(2-piperidin-1-ylethyl)-1,3-dihydro-2H-benzimidazol-2-imine IC50: 0.008 mM Trypanosoma brucei
1-biphenyl-4-yl-2-[3-[2-(diethylamino)ethyl]-2-imino-2,3-dihydro-1H-benzimidazol-1-yl]ethanone IC50: 0.025 mM Trypanosoma brucei
1-[2-imino-3-(2-morpholin-4-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-3-phenoxypropan-2-ol IC50: 0.1 mM Trypanosoma brucei
1-[2-imino-3-(2-piperidin-1-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-3,3-dimethylbutan-2-ol IC50: 0.1 mM, 66% inhibition at 0.025 mM Trypanosoma brucei
1-[2-imino-3-(2-piperidin-1-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-3-(4-methoxyphenoxy)propan-2-ol IC50: 0.016 mM Trypanosoma brucei
1-[2-imino-3-(2-piperidin-1-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-3-phenoxypropan-2-ol IC50: 0.005 mM Trypanosoma brucei
1-[2-imino-3-(morpholin-4-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-3-(4-methylphenoxy)propan-2-ol IC50: 0.1 mM Trypanosoma brucei
1-[2-imino-3-(piperidin-1-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-3-(4-methylphenoxy)propan-2-ol IC50: 0.009 mM Trypanosoma brucei
2,2'-(2-imino-1H-benzimidazole-1,3(2H)-diyl)bis(N,N-diethylethanamine) IC50: 0.059 mM Trypanosoma brucei
2-(3-benzyl-2-imino-2,3-dihydro-1H-benzimidazol-1-yl)-1-(4-chlorophenyl)ethanol IC50: 0.1 mM, 32% inhibition at 0.025 mM Trypanosoma brucei
2-[2-imino-3-(2-piperidin-1-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-1-(4-methoxyphenyl)ethanol IC50: 0.024 mM, 85% inhibition at 0.025 mM Trypanosoma brucei
2-[3-[2-(diethylamino)ethyl]-2-imino-2,3-dihydro-1H-benzimidazol-1-yl]-1-(4-methoxyphenyl)ethanone IC50: 0.007 mM, 91% inhibition at 0.025 mM Trypanosoma brucei
2-[3-[2-(diethylamino)ethyl]-2-imino-2,3-dihydro-1H-benzimidazol-1-yl]-1-(4-methylphenyl)ethanol IC50: 0.019 mM Trypanosoma brucei
2-[3-[2-(dimethylamino)ethyl]-2-imino-2,3-dihydro-1H-benzimidazol-1-yl]-1-(4-methylphenyl)ethanol IC50: 0.029 mM Trypanosoma brucei
2-[3-[2-(dimethylamino)propyl]-2-imino-2,3-dihydro-1H-benzimidazol-1-yl]-1-(4-methylphenyl)ethanol IC50: 0.035 mM Trypanosoma brucei
N,N-diethyl-2-(2-imino-3-prop-2-en-1-yl-2,3-dihydro-1H-benzimidazol-1-yl)ethanamine IC50: 0.1 mM, 31% inhibition at 0.025 mM Trypanosoma brucei
N,N-diethyl-2-[2-imino-3-(2-phenoxyethyl)-2,3-dihydro-1H-benzimidazol-1-yl]ethanamine IC50: 0.008 mM Trypanosoma brucei
N-(2-phenoxyethyl)-N'-(2-piperidin-1-ylethyl)benzene-1,2-diamine IC50: 0.1 mM Trypanosoma brucei
N-[(2E)-1-(2-phenoxyethyl)-3-(2-piperidin-1-ylethyl)-1,3-dihydro-2H-benzimidazol-2-ylidene]acetamide IC50: 0.1 mM Trypanosoma brucei

Organism

Organism UniProt Comment Textmining
Trypanosoma brucei
-
Trypanosoma brucei rhodesiense
-
Trypanosoma brucei rhodesiense
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
trypanothione + NADP+ high-throughput screening campaign of a library of 100000 lead-like compounds identified 2-iminobenzimidazoles as a novel class of trypanothione reductase inhibitors Trypanosoma brucei rhodesiense trypanothione disulfide + NADPH + H+
-
?
trypanothione disulfide + NADPH
-
Trypanosoma brucei trypanothione + NADP+
-
?

Synonyms

Synonyms Comment Organism
TR
-
Trypanosoma brucei
trypanothione reductase
-
Trypanosoma brucei
trypanothione reductase TR Trypanosoma brucei rhodesiense
trypanothione-disulfide reductase
-
Trypanosoma brucei rhodesiense

Cofactor

Cofactor Comment Organism Structure
NADPH
-
Trypanosoma brucei

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.0019
-
1,1'-[ethane-1,2-diylbis(oxyethane-2,1-diyl)]bis(3-benzyl-1,3-dihydro-2H-benzimidazol-2-imine)
-
Trypanosoma brucei rhodesiense
0.0036
-
1-(3,4-dichlorophenyl)-2-[2-imino-3-(2-piperidin-1-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]ethanol
-
Trypanosoma brucei rhodesiense
0.0054
-
1-(3,4-dichlorophenyl)-2-[3-[2-(dimethylamino)ethyl]-2-imino-2,3-dihydro-1H-benzimidazol-1-yl]ethanol
-
Trypanosoma brucei rhodesiense

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0002
-
-
Trypanosoma brucei rhodesiense 1-(3,4-dichlorophenyl)-2-[2-imino-3-(2-piperidin-1-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]ethanol
0.0006
-
-
Trypanosoma brucei rhodesiense 1-(3,4-dichlorophenyl)-2-[3-[2-(dimethylamino)ethyl]-2-imino-2,3-dihydro-1H-benzimidazol-1-yl]ethanol
0.0013
-
-
Trypanosoma brucei rhodesiense 1,1'-[ethane-1,2-diylbis(oxyethane-2,1-diyl)]bis(3-benzyl-1,3-dihydro-2H-benzimidazol-2-imine)
0.004
-
IC50: 0.004 mM Trypanosoma brucei 1-(3,4-dichlorophenyl)-2-[2-imino-3-(2-piperidin-1-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]ethanol
0.004
-
IC50: 0.004 mM Trypanosoma brucei 1-(2-phenoxyethyl)-3-(2-piperidin-1-ylethyl)-1,3-dihydro-2H-benzimidazol-2-imine
0.004
-
IC50: 0.004 mM Trypanosoma brucei 1,1'-[methanediylbis(oxyethane-2,1-diyl)]bis(3-phenyl-1,3-dihydro-2H-benzimidazol-2-imine)
0.005
-
IC50: 0.005 mM Trypanosoma brucei 1-[2-imino-3-(2-piperidin-1-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-3-phenoxypropan-2-ol
0.005
-
IC50: 0.005 mM Trypanosoma brucei 1-(2,4-dichlorophenoxy)-3-[2-imino-3-(2-piperidin-1-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]propan-2-ol
0.007
-
IC50: 0.007 mM Trypanosoma brucei 1-(3-phenoxypropyl)-3-(2-piperidin-1-ylethyl)-1,3-dihydro-2H-benzimidazol-2-imine
0.007
-
IC50: 0.007 mM, 91% inhibition at 0.025 mM Trypanosoma brucei 2-[3-[2-(diethylamino)ethyl]-2-imino-2,3-dihydro-1H-benzimidazol-1-yl]-1-(4-methoxyphenyl)ethanone
0.008
-
IC50: 0.008 mM Trypanosoma brucei N,N-diethyl-2-[2-imino-3-(2-phenoxyethyl)-2,3-dihydro-1H-benzimidazol-1-yl]ethanamine
0.008
-
IC50: 0.008 mM Trypanosoma brucei 1-(5-phenoxypentyl)-3-(2-piperidin-1-ylethyl)-1,3-dihydro-2H-benzimidazol-2-imine
0.009
-
IC50: 0.009 mM Trypanosoma brucei 1-[2-imino-3-(piperidin-1-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-3-(4-methylphenoxy)propan-2-ol
0.009
-
IC50: 0.009 mM Trypanosoma brucei 1-(3,4-dichlorophenyl)-2-[3-[2-(diethylamino)ethyl]-2-imino-2,3-dihydro-1H-benzimidazol-1-yl]ethanol
0.01
-
IC50: 0.01 mM Trypanosoma brucei 1-(3,4-dichlorophenyl)-2-[3-[2-(diethylamino)ethyl]-2-imino-2,3-dihydro-1H-benzimidazol-1-yl]ethanone
0.01
-
IC50: 0.01 mM, 92% inhibition at 0.025 mM Trypanosoma brucei 1-(3,4-dichlorophenyl)-2-[3-[2-(dimethylamino)ethyl]-2-imino-2,3-dihydro-1H-benzimidazol-1-yl]ethanol
0.016
-
IC50: 0.016 mM Trypanosoma brucei 1-[2-imino-3-(2-piperidin-1-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-3-(4-methoxyphenoxy)propan-2-ol
0.019
-
IC50: 0.019 mM Trypanosoma brucei 2-[3-[2-(diethylamino)ethyl]-2-imino-2,3-dihydro-1H-benzimidazol-1-yl]-1-(4-methylphenyl)ethanol
0.024
-
IC50: 0.024 mM, 85% inhibition at 0.025 mM Trypanosoma brucei 2-[2-imino-3-(2-piperidin-1-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-1-(4-methoxyphenyl)ethanol
0.025
-
IC50: 0.025 mM Trypanosoma brucei 1-biphenyl-4-yl-2-[3-[2-(diethylamino)ethyl]-2-imino-2,3-dihydro-1H-benzimidazol-1-yl]ethanone
0.029
-
IC50: 0.029 mM Trypanosoma brucei 2-[3-[2-(dimethylamino)ethyl]-2-imino-2,3-dihydro-1H-benzimidazol-1-yl]-1-(4-methylphenyl)ethanol
0.035
-
IC50: 0.035 mM Trypanosoma brucei 2-[3-[2-(dimethylamino)propyl]-2-imino-2,3-dihydro-1H-benzimidazol-1-yl]-1-(4-methylphenyl)ethanol
0.059
-
IC50: 0.059 mM Trypanosoma brucei 2,2'-(2-imino-1H-benzimidazole-1,3(2H)-diyl)bis(N,N-diethylethanamine)
0.1
-
IC50: 0.1 mM Trypanosoma brucei 1-[2-imino-3-(2-morpholin-4-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-3-phenoxypropan-2-ol
0.1
-
IC50: 0.1 mM Trypanosoma brucei 1-[2-imino-3-(morpholin-4-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-3-(4-methylphenoxy)propan-2-ol
0.1
-
IC50: 0.1 mM Trypanosoma brucei 1,1'-[methanediylbis(oxyethane-2,1-diyl)]bis(3-methyl-1,3-dihydro-2H-benzimidazol-2-imine)
0.1
-
IC50: 0.1 mM Trypanosoma brucei N-(2-phenoxyethyl)-N'-(2-piperidin-1-ylethyl)benzene-1,2-diamine
0.1
-
IC50: 0.1 mM Trypanosoma brucei N-[(2E)-1-(2-phenoxyethyl)-3-(2-piperidin-1-ylethyl)-1,3-dihydro-2H-benzimidazol-2-ylidene]acetamide
0.1
-
IC50: 0.1 mM Trypanosoma brucei 1-(1-methylpiperidin-3-yl)-3-(2-phenoxyethyl)-1,3-dihydro-2H-benzimidazol-2-imine
0.1
-
IC50: 0.1 mM, 31% inhibition at 0.025 mM Trypanosoma brucei N,N-diethyl-2-(2-imino-3-prop-2-en-1-yl-2,3-dihydro-1H-benzimidazol-1-yl)ethanamine
0.1
-
IC50: 0.1 mM, 32% inhibition at 0.025 mM Trypanosoma brucei 2-(3-benzyl-2-imino-2,3-dihydro-1H-benzimidazol-1-yl)-1-(4-chlorophenyl)ethanol
0.1
-
IC50: 0.1 mM, 42% inhibition at 0.025 mM Trypanosoma brucei 1-(4-bromophenyl)-2-(3-butyl-2-imino-2,3-dihydro-1H-benzimidazol-1-yl)ethanol
0.1
-
IC50: 0.1 mM, 6% inhibition at 0.025 mM Trypanosoma brucei 1-(4-ethoxyphenyl)-2-(2-imino-3-prop-2-en-1-yl-2,3-dihydro-1H-benzimidazol-1-yl)ethanol
0.1
-
IC50: 0.1 mM, 66% inhibition at 0.025 mM Trypanosoma brucei 1-[2-imino-3-(2-piperidin-1-ylethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-3,3-dimethylbutan-2-ol