Any feedback?
Information on EC 1.8.1.12 - trypanothione-disulfide reductase and Organism(s) Trypanosoma cruzi and UniProt Accession P28593
for references in articles please use BRENDA:EC1.8.1.12Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
1.8.1.12 trypanothione-disulfide reductaseIUBMB Comments
Trypanothione disulfide is the oxidized form of N1,N8-bis(glutathionyl)-spermidine from the insect-parasitic trypanosomatid Crithidia fasciculata. The enzyme from Crithidia fasciculata is a flavoprotein (FAD), whose activity is dependent on a redox-active cystine at the active centre. (cf. EC 1.8.1.7, glutathione-disulfide reductase)
Specify your search results
Word Map
- 1.8.1.12
- trypanosoma
- leishmania
- cruzi
- chagas
-
trypanosomatids
- leishmaniasis
- brucei
-
trypanocidal
-
antileishmanial
- donovani
- promastigotes
- trypanosomiasis
- infantum
- amastigotes
- fasciculata
-
antitrypanosomal
- crithidia
-
antiparasitic
-
flavoenzyme
- phenothiazine
- medicine
- epimastigotes
- nifurtimox
- amazonensis
-
antiprotozoal
- trypomastigotes
- tryparedoxin
- kinetoplastida
-
leishmanicidal
- congolense
- rhodesiense
- miltefosine
-
antimonial
- ts2
-
n1,n8-bisglutathionylspermidine
- benznidazole
- clomipramine
- glutathionylspermidine
-
antichagasic
- thioridazine
-
ovothiols
-
nitrofuran
-
trypanothione-dependent
- pharmacology
The taxonomic range for the selected organisms is: Trypanosoma cruzi
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
trypanothione reductase, li-tryr, ldtryr, trypanothione disulfide reductase, lbtryr, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
trypanothione reductase
-
N(1),N(8)-bis(glutathionyl)spermidine reductase
-
-
-
-
NADPH2:trypanothione oxidoreductase
-
-
-
-
TR
-
-
trypanothione disulfide reductase
-
-
-
-
trypanothione reductase
trypanothione reductase
-
-
-
-
trypanothione reductase
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
trypanothione + NADP+ = trypanothione disulfide + NADPH + H+
molecular modeling of inhibitor binding using X-ray data
trypanothione + NADP+ = trypanothione disulfide + NADPH + H+
substrate binding mechanism, complex structure analysis, protease-like catalytic triade and electronic induced fit
-
trypanothione + NADP+ = trypanothione disulfide + NADPH + H+
mechanistic reaction scheme, structure-function relation
-
trypanothione + NADP+ = trypanothione disulfide + NADPH + H+
mechanistic scheme for NAD(P)H:disulfide oxidoreductases
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
trypanothione:NADP+ oxidoreductase
Trypanothione disulfide is the oxidized form of N1,N8-bis(glutathionyl)-spermidine from the insect-parasitic trypanosomatid Crithidia fasciculata. The enzyme from Crithidia fasciculata is a flavoprotein (FAD), whose activity is dependent on a redox-active cystine at the active centre. (cf. EC 1.8.1.7, glutathione-disulfide reductase)
CAS REGISTRY NUMBER
COMMENTARY
102210-35-5
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
glutathionylspermidine disulfide + NADPH
2-glutathionylspermidine + NADP+
-
-
-
?
5,5'-dithiobis(N-[3-(4-methylpiperazin-1-yl)propyl]-2-nitrobenzamide) + NADPH + H+
?
-
-
-
-
r
5,5'-dithiobis(N-[3-(dimethylamino)propyl]-2-nitrobenzamide) + NADPH + H+
?
-
-
-
-
?, r
ajoene + NADPH
?
-
i.e. (E,Z)-4,5,9-trithiadodeca-1,6,11-triene-9-oxide, substrate and inhibitor
-
-
?
NADPH + trypanothione disulfide + H+
trypanothione + NADP+
-
100 microM NADPH, 105 or 93 microM trypanothione disulfide, pH 7.5, 25°C
-
-
?
trypanothione + 5,5'-dithiobis-(2-nitrobenzoic acid)
trypanothione disulfide + thionitrobenzoate
trypanothione disulfide + thio-NADPH + H+
trypanothione + thio-NADP+
-
-
-
-
r
trypanothione disulfide + NADPH + H+
trypanothione + NADP+
-
-
-
?
trypanothione disulfide + NADPH + H+
trypanothione + NADP+
-
-
-
?
glutathionylspermidine disulfide + NADPH
2-glutathionylspermidine + NADP+
-
-
-
-
?
glutathionylspermidine disulfide + NADPH
2-glutathionylspermidine + NADP+
-
-
-
r
glutathionylspermidine disulfide + NADPH
2-glutathionylspermidine + NADP+
-
-
-
r
trypanothione + 5,5'-dithiobis-(2-nitrobenzoic acid)
trypanothione disulfide + thionitrobenzoate
-
-
-
-
?
trypanothione + 5,5'-dithiobis-(2-nitrobenzoic acid)
trypanothione disulfide + thionitrobenzoate
-
inhibitors are tested using the recombinant enzyme
-
-
?
trypanothione + NADP+
trypanothione disulfide + NADPH + H+
-
-
-
-
?
trypanothione + NADP+
trypanothione disulfide + NADPH + H+
-
theoretical docking study, energy and structural output analysis is conducted on 72 nitrofuran derivatives in order to search for new and improved trypanothione reductase inhibitors
-
-
?
trypanothione + NADP+
trypanothione disulfide + NADPH + H+
-
using the recombinant enzyme
-
-
?
trypanothione disulfide + NADPH
trypanothione + NADP+
-
-
-
-
?
trypanothione disulfide + NADPH
trypanothione + NADP+
-
highly specific for
-
-
?
trypanothione disulfide + NADPH
trypanothione + NADP+
-
kex enzyme in the tryanothione-based redox metabolism of pathogenic trypanosomes
-
-
?
trypanothione disulfide + NADPH
trypanothione + NADP+
-
i.e. bisglutathionylspermidine
-
-
?
trypanothione disulfide + NADPH + H+
trypanothione + NADP+
-
-
-
-
?
additional information
?
-
serve as subversive substrates in redox cycling activity: 3,3'-[polyaminobis(carbonylalkyl)]bis(1,4-naphthoquinone) derivatives, inhibitory and substrate activity depending on spacer length
-
-
?
additional information
?
-
-
serve as subversive substrates in redox cycling activity: 3,3'-[polyaminobis(carbonylalkyl)]bis(1,4-naphthoquinone) derivatives, inhibitory and substrate activity depending on spacer length
-
-
?
additional information
?
-
-
naphthoquinones and nitrofuran derivatives are reduced, inhibition of the enzyme
-
-
?
additional information
?
-
-
chinifur increases the oxidation of the enzyme 40fold
-
-
?
additional information
?
-
-
wild-type enzyme shows transhydrogenase activity between NADPH and thio-NADP+
-
-
?
additional information
?
-
-
reduces 5,5'-dithiobis(2-nitrobenzamides)
-
-
?
additional information
?
-
-
recombinant mutants C53S, C53A, C58S: no activity with trypanothione disulfide and NADPH, but showing transhydrogenase activity between NADPH and thio-NADP+
-
-
?
additional information
?
-
-
reduces inhibitory nitrofurans, e.g. chinifur, nifuroxamide, nifuroxime and nifurprazine, and naphthoqinone derivatives
-
-
?
additional information
?
-
-
enzyme is required for maintaining the reducing intracellular environment
-
-
?
additional information
?
-
-
enzyme is required for maintaining the reducing intracellular redox equilibrium, trypanosomes lacking the enzyme are avirulent and show increased sensitivity to oxidative stress
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
trypanothione disulfide + NADPH + H+
trypanothione + NADP+
-
-
-
-
?
trypanothione disulfide + NADPH
trypanothione + NADP+
-
highly specific for
-
-
?
trypanothione disulfide + NADPH
trypanothione + NADP+
-
kex enzyme in the tryanothione-based redox metabolism of pathogenic trypanosomes
-
-
?
additional information
?
-
-
enzyme is required for maintaining the reducing intracellular environment
-
-
?
additional information
?
-
-
enzyme is required for maintaining the reducing intracellular redox equilibrium, trypanosomes lacking the enzyme are avirulent and show increased sensitivity to oxidative stress
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
FAD
-
-
394775, 394776, 394779, 394780, 394781, 394784, 394785, 394788, 394790, 394791, 394793, 394794, 394797, 394800, 394804, 394805, 394808, 394809, 710883, 724552
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1E)-1-[2-chloro-10-[3-(dimethylamino)propyl]-10,10a-dihydro-4aH-phenothiazin-8-yl]ethanone O-benzyloxime
-
(3'R,4'R)-3'-carbamoyl-1'-(2-oxo-2-[[2-(phenylsulfanyl)phenyl]amino]ethyl)-1,4'-bipiperidinium
ZINC01063940
1,1'-(10-acetyl-10,10a-dihydro-4aH-phenothiazine-2,8-diyl)diethanone
-
1,1'-[10-[3-(dimethylamino)propyl]-10,10a-dihydro-4aH-phenothiazine-2,8-diyl]diethanone
-
1-((2-(2,6-bis(phenylthio)phenyl)-1H-imidazol-5-yl)methyl)-4-methylpiperazine
36% inhibition at 0.1 mM
1-(1-(benzo[b]thiophen-2-yl)cyclohexyl)-4-((1-(2,6-bis(phenylthio)phenyl)-1H-1,2,3-triazol-4-yl)methyl)piperazine
-
1-(1-(benzo[b]thiophen-2-yl)cyclohexyl)-4-((2-(2,6-bis(phenylthio)phenyl)-1H-imidazol-4-yl)methyl)piperazine
-
1-(10-acetyl-10,10a-dihydro-4aH-phenothiazin-2-yl)-2-chloroethanone
-
1-(10-acetyl-2-chloro-10,10a-dihydro-4aH-phenothiazin-8-yl)ethanone
-
1-(2-(2,6-bis(phenylthio)phenyl)-1H-imidazol-5-yl)-N-((2-(2,6-bis(phenylthio)phenyl)-1H-imidazol-5-yl)methyl)-N,N-dimethylmethanaminium formate
86% inhibition at 0.04 mM
1-(2-(2,6-bis(phenylthio)phenyl)-1H-imidazol-5-yl)-N-(3,4-dichlorobenzyl)-N,N-dimethylmethanaminium formate
52% inhibition at 0.04 mM
1-(2-oxo-2-[[2-(phenylsulfanyl)phenyl]amino]ethyl)-4-phenylpiperazin-1-ium
ZINC05829158
1-(3,4-dichlorobenzyl)-4-(2-[[2-[(7-methoxy-2-acridinyl)amino]-6-(phenylsulfanyl)benzyl]amino]-2-oxoethyl)-1-methylpiperazin-1-ium formate
-
1-(3,4-dichlorobenzyl)-4-[2-([2-[(7-methoxy-8a,10a-dihydroacridin-2-yl)amino]-6-(naphthalen-1-ylsulfanyl)benzyl]amino)-2-oxoethyl]-1-methylpiperazin-1-ium
-
1-(3,4-dichlorobenzyl)-4-[2-([2-[(7-methoxy-8a,10a-dihydroacridin-2-yl)amino]-6-(pyridin-2-ylsulfanyl)benzyl]amino)-2-oxoethyl]-1-methylpiperazin-1-ium
-
1-(3-bromobenzyl)-5,7-dimethyl-1,3-diazoniatricyclo[3.3.1.13,7]decane
ZINC00346140
1-(4-methylphenyl)-5-oxo-N-[2-(phenylsulfanyl)phenyl]pyrrolidine-3-carboxamide
ZINC1064012
1-(4a,10a-dihydro-10H-phenothiazin-10-yl)-N,N,2-trimethylpropan-2-amine
-
1-(4a,10a-dihydro-10H-phenothiazin-10-yl)-N,N-dimethylpropan-2-amine
-
1-(8-chloro-10,11-dihydrodibenzo[b,f]thiepin-10-yl)-4-ethylpiperazinediium
ZINC00702046
1-([2-[5-bromo-2-(phenylsulfanyl)phenyl]-1H-imidazol-5-yl]methyl)-4-methylpiperazine
16% inhibition at 0.1 mM
1-benzyl-4-[[(1E)-(1-cyclohexyl-2,4,6-trioxohexahydropyrimidin-5-yl)methylidene]amino]-1-methylpiperidinium
ZINC05119716
1-[1-(1-benzothiophen-2-yl)cyclohexyl]-4-([1-[5-bromo-2-(phenylsulfanyl)phenyl]-1H-1,2,3-triazol-4-yl]methyl)piperazine
28% inhibition at 0.1 mM
1-[1-(1-benzothiophen-2-yl)cyclohexyl]-4-([2-[5-bromo-2-(phenylsulfanyl)phenyl]-1H-imidazol-4-yl]methyl)piperazine
28% inhibition at 0.1 mM
1-[2-(2-chloro-10H-phenothiazin-10-yl)-2-oxoethyl]azepanium
ZINC04866531
1-[2-chloro-10-[3-(dimethylamino)propyl]-10,10a-dihydro-4aH-phenothiazin-8-yl]ethanone
-
1-[2-[2,6-bis(phenylsulfanyl)phenyl]-1H-imidazol-5-yl]-N,N-dimethylmethanamine
25% inhibition at 0.1 mM
10-[3-(4-methylpiperidin-1-yl)propyl]-2-(trifluoromethyl)-10,10a-dihydro-4aH-phenothiazine
-
12-chloro-1,1-dimethyl-1,2,3,4,4a,13b-hexahydrodibenzo[2,3:6,7]thiepino[4,5-b]pyridin-1-ium
ZINC00347698
2-(1-cyclopentylcyclohexyl)-1-benzothiophene
61% inhibition at 0.04 mM
2-(1-[3-[2-(trifluoromethyl)-4a,10a-dihydro-10H-phenothiazin-10-yl]propyl]piperidin-4-yl)ethanol
-
2-(2,4-dioxo-1,3-diazaspiro[4.6]undec-3-yl)-N-[2-(phenylsulfanyl)phenyl]acetamide
ZINC03307332
2-(2-chloro-4a,10a-dihydro-10H-phenothiazin-10-yl)-N,N-diethyl-2-oxoethanamine
-
2-(2-chloro-4a,10a-dihydro-10H-phenothiazin-10-yl)-N,N-diethylethanamine
-
2-(2-chloro-4a,10a-dihydro-10H-phenothiazin-10-yl)-N,N-dimethylethanamine
-
2-(6-methyl-2,4-dioxo-1,3-diazaspiro[4.5]dec-3-yl)-N-[2-(phenylsulfanyl)phenyl]acetamide
ZINC2628155
2-(dimethylamino)-N-[2-[(7-methoxy-2-acridinyl)amino]-6-(phenylsulfanyl)benzyl]acetamide
-
2-([2-[(7-methoxy-8a,10a-dihydroacridin-2-yl)amino]-6-(naphthalen-1-ylsulfanyl)benzyl]amino)-N,N-dimethyl-N-[(5-nitrofuran-2-yl)methyl]-2-oxoethanaminium formate
-
2-([2-[(7-methoxy-8a,10a-dihydroacridin-2-yl)amino]-6-(pyridin-2-ylsulfanyl)benzyl]amino)-N,N-dimethyl-N-[(5-nitrofuran-2-yl)methyl]-2-oxoethanaminium formate
-
2-chloro-10-[3-[(Z)-propyldiazenyl]propyl]-10,10a-dihydro-4aH-phenothiazine
-
2-[3-(2-chloro-10H-phenothiazin-10-yl)-3-oxopropyl]octahydro-2H-pyrido[1,2-a]pyrazinediium
ZINC04427277
2-[5-[(4-methylpiperazin-1-yl)methyl]-1H-imidazol-2-yl]-N-phenyl-3-(phenylsulfanyl)aniline
58% inhibition at 0.1 mM
2-[5-[(dimethylamino)methyl]-1H-imidazol-2-yl]-N-phenyl-3-(phenylsulfanyl)aniline
42% inhibition at 0.1 mM
2-[[2-[(7-methoxy-2-acridinyl)amino]-6-(phenylsulfanyl)benzyl]amino]-N,N-dimethyl-N-(pentafluorobenzyl)-2-oxoethanaminium formate
-
2-[[2-[(7-methoxy-2-acridinyl)amino]-6-(phenylsulfanyl)benzyl]amino]-N,N-dimethyl-N-[(5-nitro-2-furyl)methyl]-2-oxoethanaminium formate
-
3,3'-[polyaminobis(carbonylalkyl)]bis(1,4-naphthoquinone) derivatives
-
-
3-(11H-dibenzo[b,e][1,4]dithiepin-11-yl)-N,N-dimethylpropan-1-aminium
ZINC00347760
3-(11H-dibenzo[b,e][1,4]oxathiepin-11-ylmethyl)-1-methylpiperidinium
ZINC04128838
3-(2-butanoyl-10H-phenothiazin-10-yl)-N,N-dimethylpropan-1-aminium
-
3-(2-carbamoyl-10H-phenothiazin-10-yl)-N,N-dimethylpropan-1-aminium
-
3-(2-chloro-4a,10a-dihydro-10H-phenothiazin-10-yl)-N,N-diethyl-3-oxopropan-1-amine
-
3-(2-chloro-4a,10a-dihydro-10H-phenothiazin-10-yl)-N,N-diethylpropan-1-amine
-
3-(2-chloro-4a,10a-dihydro-10H-phenothiazin-10-yl)-N-methylpropan-1-amine
-
3-(2-chloro-5-oxido-4a,10a-dihydro-10H-phenothiazin-10-yl)-N,N-dimethylpropan-1-amine
-
3-(2-hexanoyl-10H-phenothiazin-10-yl)-N,N-dimethylpropan-1-aminium
-
3-(4-chloro-4a,10a-dihydro-10H-phenothiazin-10-yl)-N,N-dimethylpropan-1-amine
-
3-(4a,10a-dihydro-10H-phenothiazin-10-yl)-N,N,2-trimethylpropan-1-amine
-
3-([2-[(4-tert-butylphenyl)amino]-5-fluorophenyl]amino)-N-(3,4-dichlorobenzyl)-N,N-dimethylpropan-1-aminium chloride
mixed-type inhibition
3-[2-(aminomethyl)-10H-phenothiazin-10-yl]-N,N-dimethylpropan-1-aminium
-
3-[2-(hydroxymethyl)-10H-phenothiazin-10-yl]-N,N-dimethylpropan-1-aminium
-
3-[2-(methoxycarbonyl)-10H-phenothiazin-10-yl]-N,N-dimethylpropan-1-aminium
-
3-[2-[(1E)-N-benzyl-N-oxidoethanimidoyl]-10H-phenothiazin-10-yl]-N,N-dimethylpropan-1-aminium
-
3-[2-[(E)-(hydroxyimino)methyl]-10H-phenothiazin-10-yl]-N,N-dimethylpropan-1-aminium
-
3-[[5-chloro-2-(phenylsulfanyl)phenyl]amino]-N-(3,4-dichlorobenzyl)-N,N-dimethylpropan-1-aminium chloride
-
4,15-iso-atriplicolide methacrylate
0.1 mM, 15 min, 41% inhibition
-
4-(2-chloro-4a,10a-dihydro-10H-phenothiazin-10-yl)-4-oxo-N'-phenylbutanehydrazide
-
4-(2-chloro-4a,10a-dihydro-10H-phenothiazin-10-yl)-4-oxobutanoic acid
-
4-(2-chloro-4a,10a-dihydro-10H-phenothiazin-10-yl)-N,N-diethyl-4-oxobutan-1-amine
-
4-(2-[[2-[(7-methoxy-2-acridinyl)amino]-6-(phenylsulfanyl)benzyl]amino]-2-oxoethyl)-1-methyl-1-(pentafluorobenzyl)piperazin-1-ium formate
-
4-[2-([2-[(7-methoxy-8a,10a-dihydroacridin-2-yl)amino]-6-(naphthalen-1-ylsulfanyl)benzyl]amino)-2-oxoethyl]-1-methyl-1-[(5-nitrofuran-2-yl)methyl]piperazin-1-ium formate
-
4-[2-([2-[(7-methoxy-8a,10a-dihydroacridin-2-yl)amino]-6-(pyridin-2-ylsulfanyl)benzyl]amino)-2-oxoethyl]-1-methyl-1-[(5-nitrofuran-2-yl)methyl]piperazin-1-ium formate
-
4-[6-[(3-chlorophenyl)carbamoyl]-4-oxo-1,4,5,6-tetrahydropyrimidin-2-yl]-1-methylpiperazin-1-ium
ZINC02240886
5-chloro-N-[3-(4-methylpiperazin-1-yl)propyl]-2-(phenylsulfanyl)aniline
-
6-(2-chloro-4a,10a-dihydro-10H-phenothiazin-10-yl)-N,N-diethyl-6-oxohexan-1-amine
-
7-methoxy-N-[2-([[2-(4-methylpiperazin-1-yl)ethyl]amino]methyl)-3-[[4-(trifluoromethyl)phenyl]sulfanyl]phenyl]-4a,9a-dihydroacridin-2-amine
31% inhibition at 0.02 mM
benzoyl-Gly-L-Arg-L-Arg-L-Leu-beta-naphthylamide
reversible and competitive inhibition
benzoyl-L-Leu-L-Arg-L-Arg-beta-naphthylamide
reversible and competitive inhibition
benzoyl-L-Phe-L-Val-L-Arg-7-amido-4-methylcoumarin
reversible and competitive inhibition
benzoyl-Lys-Phe-Arg-p-nitroanilide
reversible and competitive inhibition
benzyloxycarbonyl-Ala-Arg-Arg-4-methoxy-beta-naphthylamide
reversible and competitive inhibition
benzyloxycarbonyl-Gly-Gly-L-Arg-7-amido-4-methylcoumarin
reversible and competitive inhibition
benzyloxycarbonyl-L-Arg-L-Arg-4-methoxy-beta-naphthylamide
reversible and competitive inhibition
benzyloxycarbonyl-L-Arg-L-Arg-p-nitroanilide
reversible and competitive inhibition
benzyloxycarbonyl-L-Arg-p-nitroanilide
reversible and competitive inhibition
benzyloxycarbonyl-L-Lys-4-methoxy-beta-naphthylamide
reversible and competitive inhibition
cis-3-oxo-8,9b-bis-(trans-N1-(acrylamidospermidyl))-1,2,3,4,4a,9b-hexahydrodibenzofuran
-
isopropyl 2-isobutyryl-3-trifluoromethylquinoxaline-7-carboxylate 1,4-di-N-oxide
noncompetitive. IC50 values against strains NINOA and INC-5 are 0.060 microM and 0.073 microM, respectively, IC50 against human glutathione reductase is 0.050 microM
L-Phe-L-Pro-L-Arg-4-methoxy-beta-naphthylamide
reversible and competitive inhibition
N'-(2-[(7-methoxy-4a,9a-dihydroacridin-2-yl)amino]-6-[[4-(trifluoromethyl)phenyl]sulfanyl]benzyl)-N,N-dimethylethane-1,2-diamine
19% inhibition at 0.02 mM
N'-[2-[(7-methoxy-2-acridinyl)amino]-6-(phenylsulfanyl)benzyl]-N,N-dimethyl-1,2-ethanediamine
-
N'-[2-[(7-methoxy-4a,9a-dihydroacridin-2-yl)amino]-6-(pyridin-2-ylsulfanyl)benzyl]-N,N-dimethylethane-1,2-diamine
28% inhibition at 0.02 mM
N,N-dimethyl-3-(2-propanoyl-10H-phenothiazin-10-yl)propan-1-aminium
-
N,N-dimethyl-3-[2-(trifluoromethyl)-10H-phenothiazin-10-yl]propan-1-aminium
-
N,N-dimethyl-3-[2-[(1E)-N-methyl-N-oxidoethanimidoyl]-10H-phenothiazin-10-yl]propan-1-aminium
-
N-(2-[(7-methoxy-4a,9a-dihydroacridin-2-yl)amino]-6-[[4-(trifluoromethyl)phenyl]sulfanyl]benzyl)-2-(4-methylpiperazin-1-yl)acetamide
20% inhibition at 0.02 mM
N-(2-[(7-methoxy-4a,9a-dihydroacridin-2-yl)amino]-6-[[4-(trifluoromethyl)phenyl]sulfanyl]benzyl)-N2,N2-dimethylglycinamide
23% inhibition at 0.02 mM
N-(3,4-dichlorobenzyl)-2-([2-[(7-methoxy-8a,10a-dihydroacridin-2-yl)amino]-6-(naphthalen-1-ylsulfanyl)benzyl]amino)-N,N-dimethyl-2-oxoethanaminium
-
N-(3,4-dichlorobenzyl)-2-([2-[(7-methoxy-8a,10a-dihydroacridin-2-yl)amino]-6-(pyridin-2-ylsulfanyl)benzyl]amino)-N,N-dimethyl-2-oxoethanaminium
-
N-(3,4-dichlorobenzyl)-2-[[2-[(7-methoxy-2-acridinyl)amino]-6-(phenylsulfanyl)benzyl]amino]-N,N-dimethyl-2-oxoethanaminium
-
N-(3,4-dichlorobenzyl)-3-[(5-fluoro-2-[[4-(pentafluoro-l6-sulfanyl)phenyl]amino]phenyl)amino]-N,N-dimethylpropan-1-aminium chloride
mixed-type inhibition
N-(3,4-dichlorobenzyl)-3-[(5-fluoro-2-[[4-(trifluoromethyl)phenyl]amino]phenyl)amino]-N,N-dimethylpropan-1-aminium chloride
competitive inhibition
N-([2-[2,6-bis(phenylsulfanyl)phenyl]-1H-imidazol-5-yl]methyl)-N-ethylethanamine
46% inhibition at 0.1 mM
N-benzyl-4-(2-chloro-4a,10a-dihydro-10H-phenothiazin-10-yl)-4-oxobutanamide
-
N-methyl-N-(2-oxo-2-(2-(phenylthio)phenylamino)ethyl)cyclohexanaminium
-
N-[2-(2-chloro-4a,10a-dihydro-10H-phenothiazin-10-yl)-2-oxoethyl]aniline
-
N-[2-(phenylsulfanyl)phenyl]-2-[(phenylsulfonyl)amino]propanamide
ZINC00667609
N-[2-[(4-chlorophenyl)sulfanyl]phenyl]-2-(1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H-isoindol-2-yl)acetamide
ZINC02647011
N-[2-[(7-methoxy-2-acridinyl)amino]-6-(phenylsulfanyl)benzyl]-2-(4-methyl-1-piperazinyl)acetamide
-
N-[2-[(7-methoxy-2-acridinyl)amino]-6-(phenylsulfanyl)benzyl]-2-(4-methyl-1-piperazinyl)ethanimidamide
-
N-[2-[(7-methoxy-4a,9a-dihydroacridin-2-yl)amino]-6-(naphthalen-2-ylsulfanyl)benzyl]-2-(4-methylpiperazin-1-yl)acetamide
19% inhibition at 0.02 mM
N-[2-[(7-methoxy-4a,9a-dihydroacridin-2-yl)amino]-6-(naphthalen-2-ylsulfanyl)benzyl]-N2,N2-dimethylglycinamide
15% inhibition at 0.02 mM
N-[2-[(7-methoxy-4a,9a-dihydroacridin-2-yl)amino]-6-(pyridin-2-ylsulfanyl)benzyl]-2-(4-methylpiperazin-1-yl)acetamide
16% inhibition at 0.02 mM
N-[2-[(7-methoxy-4a,9a-dihydroacridin-2-yl)amino]-6-(pyridin-2-ylsulfanyl)benzyl]-N2,N2-dimethylglycinamide
12% inhibition at 0.02 mM
N1,N4-bis(3-aminopropyl)-N1-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-10-yl)-N4-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-yl)butane-1,4-diamine
-
-
N1-(3-aminopropyl)-N1-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-10-yl)butane-1,4-diamine
-
-
N1-(3-aminopropyl)-N1-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-10-yl)propane-1,3-diamine
-
-
N4-(6-chloro-2-methoxyacridin-9-yl)-N1,N1-diethylpentane-1,4-diamine
-
tert-butyl-L-Leu-L-Arg-L-Arg-7-amido-4-methylcoumarin
reversible and competitive inhibition
tert-butyl-L-Leu-L-Lys-L-Arg-7-amido-4-methylcoumarin
reversible and competitive inhibition
thioridazine
potent irreversible inhibitor. 100% inhibition at 0.010 mM
(1E)-1-(2-chlorophenyl)penta-1,4-dien-3-one
-
0.1 mM, irreversible inhibition
(22R,25R)-solasodine
-
compound is an alkaloid scaffold lead in the search for inhibitors
(22R,25S)-solanidine
-
compound is an alkaloid scaffold lead in the search for inhibitors
(22S,25S)-tomatidine
-
compound is an alkaloid scaffold lead in the search for inhibitors
(2E)-3-(5-nitrofuran-2-yl)-N-tricyclo[3.3.1.13,7]dec-1-ylprop-2-enamide
-
-
(2Z)-2-[(2E)-2-(3H-indol-3-ylidene)ethylidene]-1-methyl-1,2-dihydroquinoline
-
-
(4'-chloro-2,2':6',2''-terpyridine)platinum(II) ammine complex
-
irreversible, altering specifically the Cys52 residue in the active center, increased oxidase activity
(4-picoline) (4'-p-bromophenyl-2,2':6',2''-terpyridine)platinum(II) complex
-
irreversible, altering specifically the Cys52 residue in the active center, increased oxidase activity
(4E)-5-(2-chlorophenyl)-N,N,2,2-tetramethyl-3-oxopent-4-en-1-aminium chloride
-
0.1 mM, reversible inhibition
(4E)-5-(2-chlorophenyl)-N,N-dimethyl-3-oxopent-4-en-1-aminium chloride
-
0.1 mM, irreversible inhibition
(6-benzyloxycarbonylamino-6-[[[methyl-(2-propylamino-ethyl)-carbamoyl]-methyl]-carbamoyl]-1-[[(3-propylamino-propylcarbamoyl)-methyl]-carbamoyl]-hex-3-enyl)-carbamic acid benzyl ester
-
-
(6-benzyloxycarbonylamino-6-[[[methyl-(2-propylamino-ethyl)-carbamoyl]-methyl]-carbamoyl]-1-[[(3-propylamino-propylcarbamoyl)-methyl]-carbamoyl]-hexyl)-carbamic acid benzyl ester
-
-
1,1'-hexamethylenebis[5-(4-chlorophenyl)biguanide]
-
more than 90% inhibition at 0.1 mM
1,3-bis[3-(dimethylamino)propyl]-1,5-dihydro-2H-pyrimido[4,5-beta][1,4]benzothiazine-2,4(3H)-dione
-
no inhibition of glutathione reductase
1-(1H-indol-5-yl)-N-[(4-methylpiperazin-1-yl)methyl]methanediamine
-
0.1 mM, 31% or 39% inhibition in the presence of 0.11 mM or 0.04 mM trypanothione disulfide, respectively
1-(2-phenoxyethyl)-3-[2-(piperidin-1-yl)ethyl]-1,3-dihydro-2H-benzimidazol-2-imine
-
-
1-(3-bromothiophen-2-yl)-N-(pyridin-3-ylmethyl)methanediamine
-
0.1 mM, 15% or 14% inhibition in the presence of 0.11 mM or 0.04 mM trypanothione disulfide, respectively
1-(methylsulfanyl)-4-[3-(methylsulfanyl)-1,2,4-triazin-5-yl]-5,6,7,8-tetrahydroisoquinoline
-
-
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
-
1-[(4E)-5-(2-chlorophenyl)-3-oxopent-4-en-1-yl]piperidinium chloride
-
0.1 mM, irreversible inhibition
1-[1-(4,5-diphenylthiophen-2-yl)cyclohexyl]pyrrolidine
-
0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 15% inhibition
-
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
-
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
-
1-[2-(7-chloro-quinolin-4-ylamino)-ethyl]-1-[2-(N'',N''-dimethyl-aminomethyl)-ferrocenylmethyl]-3-p-chloro-phenyl-urea
-
ferrocenic 4-aminoquinoline urea compound 9, enzyme and growth inhibition
1-[2-(7-chloro-quinolin-4-ylamino)-ethyl]-1-[2-(N'',N''-dimethyl-aminomethyl)ferrocenylmethyl]-3-[2,6-bis-(trifluoromethyl)-phenyl]-urea
-
ferrocenic 4-aminoquinoline urea compound 8
1-[2-(7-chloro-quinolin-4-ylamino)-ethyl]-1-[2-(N'',N''-dimethylaminomethyl)-ferrocenylmethyl]-3-p-methoxyphenyl-urea
-
ferrocenic 4-aminoquinoline urea compound 6, enzyme and growth inhibition
1-[2-(7-chloro-quinolin-4-ylamino)-ethyl]-1-[2-(N'',N''-dimethylaminomethyl)-ferrocenylmethyl]-3-p-tolyl-urea
-
ferrocenic 4-aminoquinoline urea compound 5
1-[2-(7-chloro-quinolin-4-ylamino)-ethyl]-1-[2-(N'',N''-dimethylaminomethyl)-ferrocenylmethyl]-3-[2,4-bis-(trifluoromethyl)-phenyl]-urea
-
ferrocenic 4-aminoquinoline urea compound 7
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
-
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
-
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
-
2,3-Bis(3-(2-amidinohydrazono)-butyl)-1,4-naphthoquinone dihydrochloride
-
-
2-(4-[4-amino-6,7-bis[2-(dimethylamino)ethoxy]quinazolin-2-yl]piperazin-1-yl)naphthalene-1,4-dione
-
non-competitive inhibition, 79% inhibition at 0.05 mM
2-(5-nitro-2-furanylmethylidene)-N,N'-(1,4-piperazinediylbis(1,3-propanediyl))bishydrazinecarboximidamide tetrahydrobromide
-
-
2-methoxy-6-chloro-9-aminoacridine/2-hydroxyethanethiolate (2,2':6',2''-terpyridine)platinum(II) complex
-
4 chimeric compound variants, competitive and irreversible inhibition, probably Cys52 of the enzyme is specifically modified, 4'-substituted (terpyridine)platinum(II) containing complexes do not inhibit irreversibly
2-[(E)-2-(4-nitrophenyl)ethenyl]-3-phenyl-5-(phenylamino)-2,5-dihydro-1,3,4-thiadiazol-3-ium chloride
-
non-competitive inhibition, 83% inhibition at 0.001 mM
2-[4-(1H-indol-3-ylacetyl)piperazin-1-yl]-6,7-dimethoxyquinazolin-4-amine
-
23% inhibition at 0.1 mM
2-[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-5-methoxycyclohexa-2,5-diene-1,4-dione
-
non-competitive inhibition, 75% inhibition at 0.1 mM
2-[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]naphthalene-1,4-dione
-
mixed-type inhibition, 57% inhibition at 0.1 mM
3',4'-dichlorobenzyl-[5-chloro-2-(phenylsulfanylphenylamino)-propyl]-dimethylammonium chloride
-
-
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
-
3,3'-[butane-1,4-diylbis[(3-aminopropyl)imino]]bis(N-[5-chloro-2-[(4-methoxyphenyl)sulfanyl]phenyl]propanamide)
-
IC50: 0.0003 mM
3,4-dichloro-N-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-N,N-dimethylanilinium
-
-
3,4-dichloro-N-[3-([2-[(4-chlorophenyl)sulfanyl]phenyl]amino)propyl]-N,N-dimethylanilinium
-
-
3-benzyl-1-[2-(7-chloro-quinolin-4-ylamino)-ethyl]-1-[2-(N'',N''-dimethylaminomethyl)-ferrocenylmethyl]urea
-
enzyme and growth inhibition
3-Benzyl-1-[3-(7-chloro-quinolin-4-ylamino)-propyl]-1-[2-(N'',N''-dimethylaminomethyl)-ferrocenylmethyl]urea
-
-
3-Benzyl-1-[4-(7-chloro-quinolin-4-ylamino)-butyl]-1-[2-(N'',N''-dimethylaminomethyl)-ferrocenylmethyl]urea
-
-
3-Benzyl-1-[6-(7-chloro-quinolin-4-ylamino)-hexyl]-1-[2-(N'',N''-dimethylaminomethyl)-ferrocenylmethyl]urea
-
-
4,4'-bis(4-benzyloxy-3-methoxybenzimidoylamino)di-cyclohexylmethane
-
97% inhibition at 0.1 mM, in the presence of 0.1 mM trypanothione disulfide
4,6,8-trimethyl-N-(4,4,6-trimethyl-1,4-dihydropyrimidin-2-yl)quinazolin-2-amine
-
-
4-(benzofuroxan-5-ylmethyloxy)benzaldehyde amidinohydrazone
-
50% of inhibition at a inhibitor dose of 0.1 mM, 30% of inhibition at a inhibitor dose of 0.04 mM
4-(benzyloxy)-N-[3-([2-[(4-chlorophenyl)sulfanyl]phenyl]amino)propyl]-N,N-dimethylanilinium
-
-
4-[(4E)-5-(2-chlorophenyl)-3-oxopent-4-en-1-yl]morpholin-4-ium chloride
-
0.1 mM, irreversible inhibition
5,5'-dithiobis(N-[3-(4-methylpiperazin-1-yl)propyl]-2-nitrobenzamide)
-
recombinant enzyme
5-chloro-N-[3-(4-methylpiperazin-1-yl)propyl]-2-(phenylsulfanyl)aniline
-
-
5-nitro-furan-2-carboxylic acid (3-dimethylamino-propyl)-amide
reversible uncompetitive inhibition regarding substrate trypanothione disulfide, IC50 value for Trypanooma cruzi growth inhibition 0.0019 microM, EC50 value for toxicity against HeLa cells 0.074 microM
5-nitrofuran-2-carboxylic acid benzylamide
reversible uncompetitive inhibition regarding substrate trypanothione disulfide, IC50 value for Trypanooma cruzi growth inhibition 0.0015 microM, EC50 value for toxicity against HeLa cells 0.123 microM
5-nitrofuran-2-carboxylic acid dibenzylamide
reversible uncompetitive inhibition regarding substrate trypanothione disulfide, IC50 value for Trypanooma cruzi growth inhibition 0.0001 microM, EC50 value for toxicity against HeLa cells 0.078 microM
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
-
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
-
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
-
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
-
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
-
6,7-bis[2-(dimethylamino)ethoxy]-2-[4-(1H-indol-3-ylacetyl)piperazin-1-yl]quinazolin-4-amine
-
44% inhibition at 0.05 mM
6,7-dimethoxy-2-[4-[(3R)-1,2,3,4-tetrahydroisoquinolin-3-ylcarbonyl]piperazin-1-yl]quinazolin-4-amine
-
complete inhibition at 0.1 mM
6,7-dimethoxy-2-[4-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-ylcarbonyl]piperazin-1-yl]quinazolin-4-amine
-
complete inhibition at 0.1 mM
7-ethoxy-4-methyl-N-(4,4,6-trimethyl-4,5-dihydropyrimidin-2-yl)quinazolin-2-amine
-
-
7-ethyl-4-methyl-N-(4,4,6-trimethyl-4,5-dihydropyrimidin-2-yl)quinazolin-2-amine
-
-
benzofuroxan-5-carboxaldehyde thiosemicarbazone
-
19% of inhibition at a inhibitor dose of 0.1 mM, 9% of inhibition at a inhibitor dose of 0.04 mM
bis(9H-fluoren-9-ylmethyl) [(18S,23S)-3,14,17,24-tetraoxo-1,4,8,13,16-pentaazacyclotetracosane-18,23-diyl]biscarbamate
-
lack the disulfide and trypanothione's gamma-glutamyl groups have been replaced by hydrophobic aromatic moieties
bisbenzylisoquinoline alkaloids
-
e.g. cepharanthine, (-)curine, daphnoline, antioquine, limacine, cycleanine
-
cephalotaxine
-
compound is an alkaloid scaffold lead in the search for inhibitors
crude extract of Lentinus strigosus
-
100% inhibition of trypanothione reductase
-
cryptolepine
-
compound is an alkaloid scaffold lead in the search for inhibitors
dethiotrypanothione
-
trypanothione disulfide analogue 2, lack the disulfide
dibenzyl [(18S,23S)-3,14,17,24-tetraoxo-1,4,8,13,16-pentaazacyclotetracosane-18,23-diyl]biscarbamate
-
lack the disulfide and trypanothione's gamma-glutamyl groups have been replaced by hydrophobic aromatic moieties
eupomatenoid-5
-
eupomatenoid-5 decreases enzyme activity, leading to a relative increase in reactive oxygen species that triggers mitochondrial depolarization followed by an absolute increase in mitochondrial reactive oxygen and nitrogen species production through the electron transport chain. This increase in reactive oxygen and nitro-gen species induces oxidative damage, leading to parasite death
heptyl (2E)-2-[(2E)-3-(5-nitrofuran-2-yl)prop-2-en-1-ylidene]hydrazinecarboxylate
-
-
hypnophilin
-
100% inhibition of trypanothione reductase, reduces the proliferation of human peripheral blood monocluear cells, not cytotoxic for lymphocytes and monocytes
iodoacetamide
-
inhibition only of the enzyme with reduced cysteine residues in the catalytic center by alkylation
N,N'-(furan-2,5-diyldibenzene-4,1-diyl)diacetamide
-
IC50: 0.0485 mM, 54% inhibition at 0.02 mg/ml
N,N-dimethyl-N-[3-(7-methoxy-1-methyl-3,4-dihydro-9H-beta-carbolin-9-yl)propyl]amine
-
no inhibition of glutathione reductase, twenty-three heterocyclic compounds are evaluated for their potential as trypanothione reductase inhibitors
N-(3-dimethylamino-propyl)-O-[(E)-3-(3-[(E)-3-[N-(3-dimethylamino-propyl)aminooxy]-propenyl]-benzofuran-5-yl)-allyl]-hydroxylamine
-
benzofuranyl-based acyclic bis-polyamine analogue of lunarine with a planar bicyclic benzofuranyl scaffold, inhibition mechanism
N-(7-Chloro-quinolin-4-yl)-N'-[2-(N'',N''-dimethyl-aminomethyl)ferrocenylmethyl]-butane-1,4-diamine
-
-
N-(7-Chloro-quinolin-4-yl)-N'-[2-(N'',N''-dimethyl-aminomethyl)ferrocenylmethyl]-ethane-1,2-diamine
-
enzyme and growth inhibition
N-(7-Chloro-quinolin-4-yl)-N'-[2-(N'',N''-dimethyl-aminomethyl)ferrocenylmethyl]-hexane-1,6-diamine
-
-
N-(7-Chloro-quinolin-4-yl)-N'-[2-(N'',N''-dimethyl-aminomethyl)ferrocenylmethyl]-propane-1,3-diamine
-
-
N-(pyridin-3-ylmethyl)-1-thiophen-2-ylmethanediamine
-
0.1 mM, 10% inhibition in the presence of 0.11 mM or 0.04 mM trypanothione disulfide
N-[(4-chlorophenyl)(phenyl)methoxy]-8-methyl-8-azabicyclo[3.2.1]octan-3-imine
-
-
N-[(4-methylpiperazin-1-yl)methyl]-1-thiophen-2-ylmethanediamine
-
0.1 mM, 10% inhibition in the presence of 0.11 mM or 0.04 mM trypanothione disulfide
N-[2-[(naphthalen-1-ylacetyl)amino]ethyl]-4-[[(3-nitrophenyl)(oxo)acetyl]amino]piperidine-4-carboxamide
-
0.1 mM
N-[3-(4-amino-butylamino)-propyl]-O-[(E)-3-[3-((E)-3-[N-[3-(4-amino-butylamino)-propyl]aminooxy]-propenyl)-benzofuran-5-yl]-allyl]-hydroxylamine
-
benzofuranyl-based acyclic bis-polyamine analogue of lunarine with a planar bicyclic benzofuranyl scaffold, inhibition mechanism
N-[3-(4-methyl-piperazin-1-yl)-propyl]-O-[(E)-3-[3-((E)-3-[N-[3-(4-methyl-piperazin-1-yl)-propyl]aminooxy]-propenyl)-benzofuran-5-yl]-allyl]-hydroxylamine
-
benzofuranyl-based acyclic bis-polyamine analogue of lunarine with a planar bicyclic benzofuranyl scaffold, inhibition mechanism
N-[3-([2-[(4-chlorophenyl)sulfanyl]phenyl]amino)propyl]-4-(diphenylmethoxy)-N,N-dimethylanilinium
-
-
N-[3-([2-[(4-chlorophenyl)sulfanyl]phenyl]amino)propyl]-N,N-dimethylanilinium
-
-
N1,N9-bis-(L-arginyl(2,2,5,7,8-pentamethylchroman-6-sulfonamide))-norspermidine
-
non-competitive inhibitor
N1,N9-bis-(L-tryptophanyl-L-arginyl(2,2,5,7,8-pentamethylchroman-6-sulfonamide))-norspermidine
-
non-competitive inhibitor
N1,N9-bis-(L-tryptophanyl-L-arginyl)-norspermidine
-
non-competitive inhibitor
N1-L-arginyl(2,2,5,7,8-pentamethylchroman-6-sulfonamide)-N9-acetyl-norspermidine
-
-
N1-L-arginyl(2,2,5,7,8-pentamethylchroman-6-sulfonamide)-N9-hexanoyl-norspermidine
-
-
N1-L-arginyl(2,2,5,7,8-pentamethylchroman-6-sulfonamide)-N9-L-arginyl-norspermidine
-
non-competitive inhibitor
N1-L-tryptophanyl-L-arginyl(2,2,5,7,8-pentamethylchroman-6-sulfonamide)-N9-acetyl-norspermidine
-
-
N1-L-tryptophanyl-L-arginyl(2,2,5,7,8-pentamethylchroman-6-sulfonamide)-N9-hexanoyl-norspermidine
-
-
N1-L-tryptophanyl-L-arginyl(2,2,5,7,8-pentamethylchroman-6-sulfonamide)-norspermidine
-
-
N1-L-tryptophanyl-L-arginyl-N9-L-tryptophanyl-L-arginyl(2,2,5,7,8-pentamethylchroman-6-sulfonamide)-norspermidine
-
non-competitive inhibitor
N4-allyl benzofuroxan-5-carboxaldehyde thiosemicarbazone
-
9% of inhibition at a inhibitor dose of 0.1 mM, 13% of inhibition at a inhibitor dose of 0.04 mM
quebrachamine
-
compound is an alkaloid scaffold lead in the search for inhibitors
quinacrine mustard
-
enzyme and inhibitor first forms a reversible complex, then irreversible inactivation of NADPH-reduced and oxidized enzyme occurs, enzyme contains 2 interacting binding sites in the active site for the inhibitors, 2 inhibitor molecules per enzyme monomer are bound, addition of 2-mercaptoethanol prevents inactivation up to 25 mM, clomipramine strongly protects th enzyme from inactivation
spermidine derivatives
-
derivatives of 2-amino-diphenylsulfide + phenothiazine
-
spermine derivatives
-
derivatives of 2-amino-diphenylsulfide + phenothiazine
-
[6-benzyloxycarbonylamino-1,6-bis-(dimethylcarbamoylmethyl-carbamoyl)-hex-3-enyl]-carbamic acid benzyl ester
-
-
[6-benzyloxycarbonylamino-1,6-bis-(dimethylcarbamoylmethyl-carbamoyl)-hexyl]-carbamic acid benzyl ester
-
-
3-Chloro-5-(3-(dimethylamino)propyl)-10,11-dihydro-5H-dibenz(b,f)azepine
-
-
3-Chloro-5-(3-(dimethylamino)propyl)-10,11-dihydro-5H-dibenz(b,f)azepine
-
IC50: 0.0065 mM
ajoene
-
i.e. (E,Z)-4,5,9-trithiadodeca-1,6,11-triene-9-oxide, natural compound from garlic, Allium sativum, covalent inhibition, but also substrate
lunarine
-
Lunaria derived alkaloid with a unusual 3-oxohexahydrodibenzofuranyl tricyclic scaffold, competitive, reversible formation of a covalent adduct between Cys53 and one of the alpha,beta-unsaturated amide groups of lunarine, mechanism, enzyme needs to be in reduced state
additional information
a virtual screening of a library of thiadiazine derivatives against trypanothione reductase using molecular docking is performed. Thiadiazine-based compounds are identified as plausible candidates to selectively inhibit the parasitic enzyme
-
additional information
-
antiparasitic drugs designed using three-dimensional structure
-
additional information
-
increasing ionic strength leads to inhibition, e.g. with NaCl, KCl, (NH4)SO4, HEPES
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
activity is dependent on a redox-active cysteine at the active centre
-
additional information
-
activity is dependent on a redox-active cysteine at the active centre
-
additional information
-
activity is dependent on a redox-active cysteine at the active centre
-
additional information
-
activity is dependent on a redox-active cysteine at the active centre
-
additional information
-
activity is dependent on a redox-active cysteine at the active centre
-
additional information
-
activity is dependent on a redox-active cysteine at the active centre
-
additional information
-
activity is dependent on a redox-active cysteine at the active centre
-
additional information
-
activity is dependent on a redox-active cysteine at the active centre
-
additional information
-
activity is dependent on a redox-active cysteine at the active centre
-
additional information
-
activity is dependent on a redox-active cysteine at the active centre
-
additional information
-
activity is dependent on a redox-active cysteine at the active centre
-
additional information
-
activity is dependent on a redox-active cysteine at the active centre
-
additional information
-
activity is dependent on a redox-active cysteine at the active centre
-
additional information
-
activity is dependent on a redox-active cysteine at the active centre
-
additional information
-
activity is dependent on a redox-active cysteine at the active centre
-
additional information
-
activity is dependent on a redox-active cysteine at the active centre
-
additional information
-
activity is dependent on a redox-active cysteine at the active centre
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.3
5,5'-dithiobis(N-[3-(4-methylpiperazin-1-yl)propyl]-2-nitrobenzamide)
-
recombinant enzyme
0.035
5,5'-dithiobis(N-[3-(dimethylamino)propyl]-2-nitrobenzamide)
-
recombinant enzyme
additional information
additional information
-
Km dependent on assay conditions
-
0.022 - 0.275
glutathionylspermidine disulfide
-
dependent on buffer system
0.0015
trypanothione disulfide
-
apparent value, in the presence of 0.05 mM DTNB and 0.15 mM NADPH, in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) BSA, and 0.05% (v/v) Tween 20, pH 7.5, at 22°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
125
5,5'-dithiobis(N-[3-(4-methylpiperazin-1-yl)propyl]-2-nitrobenzamide)
-
recombinant enzyme
125
5,5'-dithiobis(N-[3-(dimethylamino)propyl]-2-nitrobenzamide)
-
recombinant enzyme
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0011
1-(1-(benzo[b]thiophen-2-yl)cyclohexyl)-4-((1-(2,6-bis(phenylthio)phenyl)-1H-1,2,3-triazol-4-yl)methyl)piperazine
at 25°C, pH not specified in the publication
0.002
1-(2-(2,6-bis(phenylthio)phenyl)-1H-imidazol-5-yl)-N-((2-(2,6-bis(phenylthio)phenyl)-1H-imidazol-5-yl)methyl)-N,N-dimethylmethanaminium formate
at 25°C, pH not specified in the publication
0.005
1-(2-(2,6-bis(phenylthio)phenyl)-1H-imidazol-5-yl)-N-(3,4-dichlorobenzyl)-N,N-dimethylmethanaminium formate
at 25°C, pH not specified in the publication
0.216
1-(4a,10a-dihydro-10H-phenothiazin-10-yl)-N,N-dimethylpropan-2-amine
-
0.023
10-[3-(4-methylpiperidin-1-yl)propyl]-2-(trifluoromethyl)-10,10a-dihydro-4aH-phenothiazine
-
0.0212
2-(1-[3-[2-(trifluoromethyl)-4a,10a-dihydro-10H-phenothiazin-10-yl]propyl]piperidin-4-yl)ethanol
-
0.0187
2-chloro-10-[3-[(Z)-propyldiazenyl]propyl]-10,10a-dihydro-4aH-phenothiazine
-
0.0108
3-(2-chloro-10H-phenothiazin-10-yl)-N,N-dimethylpropan-1-aminium
-
0.127
3-(4a,10a-dihydro-10H-phenothiazin-10-yl)-N,N,2-trimethylpropan-1-amine
-
0.084 - 0.158
3-([2-[(4-tert-butylphenyl)amino]-5-fluorophenyl]amino)-N-(3,4-dichlorobenzyl)-N,N-dimethylpropan-1-aminium chloride
0.0065
clomipramine
pH and temperature not specified in the publication
0.0302
N,N-dimethyl-3-[2-(trifluoromethyl)-10H-phenothiazin-10-yl]propan-1-aminium
-
0.028 - 0.72
N-(3,4-dichlorobenzyl)-3-[(5-fluoro-2-[[4-(pentafluoro-l6-sulfanyl)phenyl]amino]phenyl)amino]-N,N-dimethylpropan-1-aminium chloride
0.03
(6-benzyloxycarbonylamino-6-[[[methyl-(2-propylamino-ethyl)-carbamoyl]-methyl]-carbamoyl]-1-[[(3-propylamino-propylcarbamoyl)-methyl]-carbamoyl]-hex-3-enyl)-carbamic acid benzyl ester
-
-
0.048
(6-benzyloxycarbonylamino-6-[[[methyl-(2-propylamino-ethyl)-carbamoyl]-methyl]-carbamoyl]-1-[[(3-propylamino-propylcarbamoyl)-methyl]-carbamoyl]-hexyl)-carbamic acid benzyl ester
-
-
0.0269
1,3-bis[3-(dimethylamino)propyl]-1,5-dihydro-2H-pyrimido[4,5-beta][1,4]benzothiazine-2,4(3H)-dione
-
-
0.011
2-(4-[4-amino-6,7-bis[2-(dimethylamino)ethoxy]quinazolin-2-yl]piperazin-1-yl)naphthalene-1,4-dione
-
-
0.15
2-amino-4-chlorophenyl phenyl sulfide
-
at pH 7.25, 25°C in 0.02 M HEPES buffer containing 0.15 M KCl, 1 mM EDTA, 0.1 mM NADPH
0.032
2-[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-5-methoxycyclohexa-2,5-diene-1,4-dione
-
-
0.0075
2-[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]naphthalene-1,4-dione
-
-
0.0017
3',4'-dichlorobenzyl-[5-chloro-2-(phenylsulfanylphenylamino)-propyl]-dimethylammonium chloride
-
at pH 7.25, 25°C in 0.02 M HEPES buffer containing 0.15 M KCl, 1 mM EDTA, 0.1 mM NADPH
0.00044
3,4-dichloro-N-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-N,N-dimethylanilinium
-
0.0008 mM, at pH 7.25, 25°C in 0.02 M HEPES buffer containing 0.15 M KCl, 1 mM EDTA, 0.1 mM NADPH
0.00169
3,4-dichloro-N-[3-([2-[(4-chlorophenyl)sulfanyl]phenyl]amino)propyl]-N,N-dimethylanilinium
-
at pH 7.25, 25°C in 0.02 M HEPES buffer containing 0.15 M KCl, 1 mM EDTA, 0.1 mM NADPH
0.0065
3-Chloro-5-(3-(dimethylamino)propyl)-10,11-dihydro-5H-dibenz(b,f)azepine
-
at pH 7.25, 25°C in 0.02 M HEPES buffer containing 0.15 M KCl, 1 mM EDTA, 0.1 mM NADPH
0.002
4,4'-bis(4-benzyloxy-3-methoxybenzimidoylamino)di-cyclohexylmethane
-
-
0.0066
4-(benzyloxy)-N-[3-([2-[(4-chlorophenyl)sulfanyl]phenyl]amino)propyl]-N,N-dimethylanilinium
-
at pH 7.25, 25°C in 0.02 M HEPES buffer containing 0.15 M KCl, 1 mM EDTA, 0.1 mM NADPH
0.027
5-chloro-N-[3-(4-methylpiperazin-1-yl)propyl]-2-(phenylsulfanyl)aniline
-
at pH 7.25, 25°C in 0.02 M HEPES buffer containing 0.15 M KCl, 1 mM EDTA, 0.1 mM NADPH
0.118
5-nitro-furan-2-carboxylic acid (3-dimethylamino-propyl)-amide
pH 7.5, 30°C
0.0936
amitryptyline
-
at pH 7.25, 25°C in 0.02 M HEPES buffer containing 0.15 M KCl, 1 mM EDTA, 0.1 mM NADPH
0.016
bis(9H-fluoren-9-ylmethyl) [(18S,23S)-3,14,17,24-tetraoxo-1,4,8,13,16-pentaazacyclotetracosane-18,23-diyl]biscarbamate
-
-
0.0108
chlorpromazine
-
at pH 7.25, 25°C in 0.02 M HEPES buffer containing 0.15 M KCl, 1 mM EDTA, 0.1 mM NADPH
0.0086
clomipramine
-
recombinant enzyme, with 5,5'-dithiobis(N-[3-(dimethylamino)propyl]-2-nitrobenzamide)
0.145
dibenzyl [(18S,23S)-3,14,17,24-tetraoxo-1,4,8,13,16-pentaazacyclotetracosane-18,23-diyl]biscarbamate
-
-
0.066
N'-[5-chloro-2-(phenylsulfanyl)phenyl]-N,N-dimethylpropane-1,3-diamine
-
at pH 7.25, 25°C in 0.02 M HEPES buffer containing 0.15 M KCl, 1 mM EDTA, 0.1 mM NADPH
0.035
N,N-dimethyl-N-[3-(7-methoxy-1-methyl-3,4-dihydro-9H-beta-carbolin-9-yl)propyl]amine
-
-
0.0246
N-[2-[(4-chlorophenyl)sulfanyl]phenyl]-2-phenylacetamide
-
at pH 7.25, 25°C in 0.02 M HEPES buffer containing 0.15 M KCl, 1 mM EDTA, 0.1 mM NADPH
0.0428
N-[2-[(4-chlorophenyl)sulfanyl]phenyl]-4-nitrobenzamide
-
at pH 7.25, 25°C in 0.02 M HEPES buffer containing 0.15 M KCl, 1 mM EDTA, 0.1 mM NADPH
0.0245
N-[2-[(4-chlorophenyl)sulfanyl]phenyl]benzamide
-
at pH 7.25, 25°C in 0.02 M HEPES buffer containing 0.15 M KCl, 1 mM EDTA, 0.1 mM NADPH
0.0113
N-[2-[(4-chlorophenyl)sulfanyl]phenyl]butanamide
-
at pH 7.25, 25°C in 0.02 M HEPES buffer containing 0.15 M KCl, 1 mM EDTA, 0.1 mM NADPH
0.02
N-[2-[(4-chlorophenyl)sulfanyl]phenyl]propanamide
-
at pH 7.25, 25°C in 0.02 M HEPES buffer containing 0.15 M KCl, 1 mM EDTA, 0.1 mM NADPH
0.009
N-[2-[(naphthalen-1-ylacetyl)amino]ethyl]-4-[[(3-nitrophenyl)(oxo)acetyl]amino]piperidine-4-carboxamide
-
mixed type inhibitor, 0.1 mM
0.0053
N-[3-([2-[(4-chlorophenyl)sulfanyl]phenyl]amino)propyl]-4-(diphenylmethoxy)-N,N-dimethylanilinium
-
at pH 7.25, 25°C in 0.02 M HEPES buffer containing 0.15 M KCl, 1 mM EDTA, 0.1 mM NADPH
0.0142
N-[3-([2-[(4-chlorophenyl)sulfanyl]phenyl]amino)propyl]-N,N-dimethylanilinium
-
at pH 7.25, 25°C in 0.02 M HEPES buffer containing 0.15 M KCl, 1 mM EDTA, 0.1 mM NADPH
0.003
N1,N9-bis-(L-arginyl(2,2,5,7,8-pentamethylchroman-6-sulfonamide))-norspermidine
-
-
0.00016
N1,N9-bis-(L-tryptophanyl-L-arginyl(2,2,5,7,8-pentamethylchroman-6-sulfonamide))-norspermidine
-
-
0.069
N1-L-arginyl(2,2,5,7,8-pentamethylchroman-6-sulfonamide)-N9-acetyl-norspermidine
-
-
0.007
N1-L-arginyl(2,2,5,7,8-pentamethylchroman-6-sulfonamide)-N9-hexanoyl-norspermidine
-
-
0.011
N1-L-arginyl(2,2,5,7,8-pentamethylchroman-6-sulfonamide)-N9-L-arginyl-norspermidine
-
-
0.131
N1-L-arginyl(2,2,5,7,8-pentamethylchroman-6-sulfonamide)-norspermidine
-
-
0.012
N1-L-tryptophanyl-L-arginyl(2,2,5,7,8-pentamethylchroman-6-sulfonamide)-N9-acetyl-norspermidine
-
-
0.006
N1-L-tryptophanyl-L-arginyl(2,2,5,7,8-pentamethylchroman-6-sulfonamide)-N9-hexanoyl-norspermidine
-
-
0.009
N1-L-tryptophanyl-L-arginyl(2,2,5,7,8-pentamethylchroman-6-sulfonamide)-norspermidine
-
-
0.00022
N1-L-tryptophanyl-L-arginyl-N9-L-tryptophanyl-L-arginyl(2,2,5,7,8-pentamethylchroman-6-sulfonamide)-norspermidine
-
-
0.023
Trifluperazine
-
at pH 7.25, 25°C in 0.02 M HEPES buffer containing 0.15 M KCl, 1 mM EDTA, 0.1 mM NADPH
0.074
[6-benzyloxycarbonylamino-1,6-bis-(dimethylcarbamoylmethyl-carbamoyl)-hex-3-enyl]-carbamic acid benzyl ester
-
-
0.091
[6-benzyloxycarbonylamino-1,6-bis-(dimethylcarbamoylmethyl-carbamoyl)-hexyl]-carbamic acid benzyl ester
-
-
0.084
3-([2-[(4-tert-butylphenyl)amino]-5-fluorophenyl]amino)-N-(3,4-dichlorobenzyl)-N,N-dimethylpropan-1-aminium chloride
competitive inhibition, at 25°C
0.158
3-([2-[(4-tert-butylphenyl)amino]-5-fluorophenyl]amino)-N-(3,4-dichlorobenzyl)-N,N-dimethylpropan-1-aminium chloride
uncompetitive inhibition, at 25°C
0.028
N-(3,4-dichlorobenzyl)-3-[(5-fluoro-2-[[4-(pentafluoro-l6-sulfanyl)phenyl]amino]phenyl)amino]-N,N-dimethylpropan-1-aminium chloride
competitive inhibition, at 25°C
0.72
N-(3,4-dichlorobenzyl)-3-[(5-fluoro-2-[[4-(pentafluoro-l6-sulfanyl)phenyl]amino]phenyl)amino]-N,N-dimethylpropan-1-aminium chloride
uncompetitive inhibition, at 25°C
additional information
additional information
-
derivatives of 2-amino-diphenylsulfide + phenothiazine
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.1
(3'R,4'R)-3'-carbamoyl-1'-(2-oxo-2-[[2-(phenylsulfanyl)phenyl]amino]ethyl)-1,4'-bipiperidinium
Trypanosoma cruzi
IC50 above 0.1 mM
0.115
1-((2-(2,6-bis(phenylthio)phenyl)-1H-imidazol-5-yl)methyl)-4-methylpiperazine
Trypanosoma cruzi
at 25°C, pH not specified in the publication
0.05212
1-(1-(benzo[b]thiophen-2-yl)cyclohexyl)-4-((1-(2,6-bis(phenylthio)phenyl)-1H-1,2,3-triazol-4-yl)methyl)piperazine
Trypanosoma cruzi
at 25°C, pH not specified in the publication
0.00233
1-(1-(benzo[b]thiophen-2-yl)cyclohexyl)-4-((2-(2,6-bis(phenylthio)phenyl)-1H-imidazol-4-yl)methyl)piperazine
Trypanosoma cruzi
at 25°C, pH not specified in the publication
0.00633
1-(2-(2,6-bis(phenylthio)phenyl)-1H-imidazol-5-yl)-N-((2-(2,6-bis(phenylthio)phenyl)-1H-imidazol-5-yl)methyl)-N,N-dimethylmethanaminium formate
Trypanosoma cruzi
at 25°C, pH not specified in the publication
0.0024
1-(2-(2,6-bis(phenylthio)phenyl)-1H-imidazol-5-yl)-N-(3,4-dichlorobenzyl)-N,N-dimethylmethanaminium formate
Trypanosoma cruzi
at 25°C, pH not specified in the publication
0.1
1-(2-oxo-2-[[2-(phenylsulfanyl)phenyl]amino]ethyl)-4-phenylpiperazin-1-ium
Trypanosoma cruzi
IC50 above 0.1 mM
0.0695
1-(3,4-dichlorobenzyl)-4-[2-([2-[(7-methoxy-8a,10a-dihydroacridin-2-yl)amino]-6-(naphthalen-1-ylsulfanyl)benzyl]amino)-2-oxoethyl]-1-methylpiperazin-1-ium
Trypanosoma cruzi
at 25°C
0.0512
1-(3,4-dichlorobenzyl)-4-[2-([2-[(7-methoxy-8a,10a-dihydroacridin-2-yl)amino]-6-(pyridin-2-ylsulfanyl)benzyl]amino)-2-oxoethyl]-1-methylpiperazin-1-ium
Trypanosoma cruzi
at 25°C
0.1
1-(3-bromobenzyl)-5,7-dimethyl-1,3-diazoniatricyclo[3.3.1.13,7]decane
Trypanosoma cruzi
IC50 above 0.1 mM
0.1
1-(4-methylphenyl)-5-oxo-N-[2-(phenylsulfanyl)phenyl]pyrrolidine-3-carboxamide
Trypanosoma cruzi
IC50 above 0.1 mM
0.0291
1-(8-chloro-10,11-dihydrodibenzo[b,f]thiepin-10-yl)-4-ethylpiperazinediium
Trypanosoma cruzi
-
0.0759
1-([2-[5-bromo-2-(phenylsulfanyl)phenyl]-1H-imidazol-5-yl]methyl)-4-methylpiperazine
Trypanosoma cruzi
at 25°C, pH not specified in the publication
0.0452
1-benzyl-4-[[(1E)-(1-cyclohexyl-2,4,6-trioxohexahydropyrimidin-5-yl)methylidene]amino]-1-methylpiperidinium
Trypanosoma cruzi
-
0.0106
1-[1-(1-benzothiophen-2-yl)cyclohexyl]-4-([1-[5-bromo-2-(phenylsulfanyl)phenyl]-1H-1,2,3-triazol-4-yl]methyl)piperazine
Trypanosoma cruzi
at 25°C, pH not specified in the publication
0.00424
1-[1-(1-benzothiophen-2-yl)cyclohexyl]-4-([2-[5-bromo-2-(phenylsulfanyl)phenyl]-1H-imidazol-4-yl]methyl)piperazine
Trypanosoma cruzi
at 25°C, pH not specified in the publication
0.0787
1-[2-(2-chloro-10H-phenothiazin-10-yl)-2-oxoethyl]azepanium
Trypanosoma cruzi
-
0.0122
1-[2-[2,6-bis(phenylsulfanyl)phenyl]-1H-imidazol-5-yl]-N,N-dimethylmethanamine
Trypanosoma cruzi
at 25°C, pH not specified in the publication
0.0753
12-chloro-1,1-dimethyl-1,2,3,4,4a,13b-hexahydrodibenzo[2,3:6,7]thiepino[4,5-b]pyridin-1-ium
Trypanosoma cruzi
-
0.1
2-(2,4-dioxo-1,3-diazaspiro[4.6]undec-3-yl)-N-[2-(phenylsulfanyl)phenyl]acetamide
Trypanosoma cruzi
IC50 above 0.1 mM
0.0844
2-(6-methyl-2,4-dioxo-1,3-diazaspiro[4.5]dec-3-yl)-N-[2-(phenylsulfanyl)phenyl]acetamide
Trypanosoma cruzi
-
0.0783
2-([2-[(7-methoxy-8a,10a-dihydroacridin-2-yl)amino]-6-(naphthalen-1-ylsulfanyl)benzyl]amino)-N,N-dimethyl-N-[(5-nitrofuran-2-yl)methyl]-2-oxoethanaminium formate
Trypanosoma cruzi
at 25°C
0.0309
2-([2-[(7-methoxy-8a,10a-dihydroacridin-2-yl)amino]-6-(pyridin-2-ylsulfanyl)benzyl]amino)-N,N-dimethyl-N-[(5-nitrofuran-2-yl)methyl]-2-oxoethanaminium formate
Trypanosoma cruzi
at 25°C
0.0354
2-[3-(2-chloro-10H-phenothiazin-10-yl)-3-oxopropyl]octahydro-2H-pyrido[1,2-a]pyrazinediium
Trypanosoma cruzi
-
0.0539
2-[5-[(4-methylpiperazin-1-yl)methyl]-1H-imidazol-2-yl]-N-phenyl-3-(phenylsulfanyl)aniline
Trypanosoma cruzi
at 25°C, pH not specified in the publication
0.162
2-[5-[(dimethylamino)methyl]-1H-imidazol-2-yl]-N-phenyl-3-(phenylsulfanyl)aniline
Trypanosoma cruzi
at 25°C, pH not specified in the publication
0.0367
3-(11H-dibenzo[b,e][1,4]dithiepin-11-yl)-N,N-dimethylpropan-1-aminium
Trypanosoma cruzi
-
0.0115
3-(11H-dibenzo[b,e][1,4]oxathiepin-11-ylmethyl)-1-methylpiperidinium
Trypanosoma cruzi
-
0.0268
4-[2-([2-[(7-methoxy-8a,10a-dihydroacridin-2-yl)amino]-6-(naphthalen-1-ylsulfanyl)benzyl]amino)-2-oxoethyl]-1-methyl-1-[(5-nitrofuran-2-yl)methyl]piperazin-1-ium formate
Trypanosoma cruzi
at 25°C
0.0246
4-[2-([2-[(7-methoxy-8a,10a-dihydroacridin-2-yl)amino]-6-(pyridin-2-ylsulfanyl)benzyl]amino)-2-oxoethyl]-1-methyl-1-[(5-nitrofuran-2-yl)methyl]piperazin-1-ium formate
Trypanosoma cruzi
at 25°C
0.1
4-[6-[(3-chlorophenyl)carbamoyl]-4-oxo-1,4,5,6-tetrahydropyrimidin-2-yl]-1-methylpiperazin-1-ium
Trypanosoma cruzi
IC50 above 0.1 mM
0.1
6-(naphthalen-2-ylamino)-6-oxohexane-1,5-diaminium
Trypanosoma cruzi
IC50 above 0.1 mM
0.019
7-methoxy-N-[2-([[2-(4-methylpiperazin-1-yl)ethyl]amino]methyl)-3-[[4-(trifluoromethyl)phenyl]sulfanyl]phenyl]-4a,9a-dihydroacridin-2-amine
Trypanosoma cruzi
at 25°C
0.0063
chlorpromazine
Trypanosoma cruzi
pH and temperature not specified in the publication
0.0038
clomipramine
Trypanosoma cruzi
pH and temperature not specified in the publication
0.0243
N'-(2-[(7-methoxy-4a,9a-dihydroacridin-2-yl)amino]-6-[[4-(trifluoromethyl)phenyl]sulfanyl]benzyl)-N,N-dimethylethane-1,2-diamine
Trypanosoma cruzi
at 25°C
0.0342
N'-[2-[(7-methoxy-4a,9a-dihydroacridin-2-yl)amino]-6-(pyridin-2-ylsulfanyl)benzyl]-N,N-dimethylethane-1,2-diamine
Trypanosoma cruzi
at 25°C
0.0093
N-(2-[(7-methoxy-4a,9a-dihydroacridin-2-yl)amino]-6-[[4-(trifluoromethyl)phenyl]sulfanyl]benzyl)-2-(4-methylpiperazin-1-yl)acetamide
Trypanosoma cruzi
at 25°C
0.104
N-(2-[(7-methoxy-4a,9a-dihydroacridin-2-yl)amino]-6-[[4-(trifluoromethyl)phenyl]sulfanyl]benzyl)-N2,N2-dimethylglycinamide
Trypanosoma cruzi
at 25°C
0.0469
N-(3,4-dichlorobenzyl)-2-([2-[(7-methoxy-8a,10a-dihydroacridin-2-yl)amino]-6-(naphthalen-1-ylsulfanyl)benzyl]amino)-N,N-dimethyl-2-oxoethanaminium
Trypanosoma cruzi
at 25°C
0.0566
N-(3,4-dichlorobenzyl)-2-([2-[(7-methoxy-8a,10a-dihydroacridin-2-yl)amino]-6-(pyridin-2-ylsulfanyl)benzyl]amino)-N,N-dimethyl-2-oxoethanaminium
Trypanosoma cruzi
at 25°C
0.0116
N-([2-[2,6-bis(phenylsulfanyl)phenyl]-1H-imidazol-5-yl]methyl)-N-ethylethanamine
Trypanosoma cruzi
at 25°C, pH not specified in the publication
0.1
N-[2-(phenylsulfanyl)phenyl]-2-[(phenylsulfonyl)amino]propanamide
Trypanosoma cruzi
IC50 above 0.1 mM
0.1
N-[2-[(4-chlorophenyl)sulfanyl]phenyl]-2-(1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H-isoindol-2-yl)acetamide
Trypanosoma cruzi
IC50 above 0.1 mM
0.0093
N-[2-[(7-methoxy-4a,9a-dihydroacridin-2-yl)amino]-6-(naphthalen-2-ylsulfanyl)benzyl]-2-(4-methylpiperazin-1-yl)acetamide
Trypanosoma cruzi
at 25°C
0.121
N-[2-[(7-methoxy-4a,9a-dihydroacridin-2-yl)amino]-6-(naphthalen-2-ylsulfanyl)benzyl]-N2,N2-dimethylglycinamide
Trypanosoma cruzi
at 25°C
0.0158
N-[2-[(7-methoxy-4a,9a-dihydroacridin-2-yl)amino]-6-(pyridin-2-ylsulfanyl)benzyl]-2-(4-methylpiperazin-1-yl)acetamide
Trypanosoma cruzi
at 25°C
0.0576
N-[2-[(7-methoxy-4a,9a-dihydroacridin-2-yl)amino]-6-(pyridin-2-ylsulfanyl)benzyl]-N2,N2-dimethylglycinamide
Trypanosoma cruzi
at 25°C
0.0074
prochlorperazine
Trypanosoma cruzi
pH and temperature not specified in the publication
0.0075
triflupromizine
Trypanosoma cruzi
pH and temperature not specified in the publication
-
0.0021
(2E)-3-(5-nitrofuran-2-yl)-N-tricyclo[3.3.1.13,7]dec-1-ylprop-2-enamide
Trypanosoma cruzi
-
-
0.023
(2Z)-2-[(2E)-2-(3H-indol-3-ylidene)ethylidene]-1-methyl-1,2-dihydroquinoline
Trypanosoma cruzi
-
in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.002
1-(1-benzylpiperidin-4-yl)-3-phenylthiourea
Trypanosoma cruzi
-
in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.1
1-(1-benzylpiperidin-4-yl)-3-pyridin-3-ylthiourea
Trypanosoma cruzi
-
IC50 above 0.1 mM, in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.1
1-(1-phenylpiperidin-4-yl)-3-propylthiourea
Trypanosoma cruzi
-
IC50 above 0.1 mM, in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.009
1-(2-phenoxyethyl)-3-[2-(piperidin-1-yl)ethyl]-1,3-dihydro-2H-benzimidazol-2-imine
Trypanosoma cruzi
-
in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.1
1-(4,6,8-trimethylquinazolin-2-yl)guanidine
Trypanosoma cruzi
-
IC50 above 0.1 mM, in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.1
1-(4-methylquinazolin-2-yl)guanidine
Trypanosoma cruzi
-
IC50 above 0.1 mM, in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.1
1-(methylsulfanyl)-4-[3-(methylsulfanyl)-1,2,4-triazin-5-yl]-5,6,7,8-tetrahydroisoquinoline
Trypanosoma cruzi
-
IC50 above 0.1 mM, in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.033
1-phenyl-3-(1-phenylpiperidin-4-yl)thiourea
Trypanosoma cruzi
-
in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.1
1-phenyl-3-[1-(pyridin-3-yl)piperidin-4-yl]urea
Trypanosoma cruzi
-
IC50 above 0.1 mM, in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.0032
1-[2-(4-methylpiperazin-1-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole
Trypanosoma cruzi
-
pH and temperature not specified in the publication
-
0.0025
1-[2-(7-chloro-quinolin-4-ylamino)-ethyl]-1-[2-(N'',N''-dimethyl-aminomethyl)-ferrocenylmethyl]-3-p-chloro-phenyl-urea
Trypanosoma cruzi
-
-
0.002
1-[2-(7-chloro-quinolin-4-ylamino)-ethyl]-1-[2-(N'',N''-dimethyl-aminomethyl)ferrocenylmethyl]-3-[2,6-bis-(trifluoromethyl)-phenyl]-urea
Trypanosoma cruzi
-
-
0.0023
1-[2-(7-chloro-quinolin-4-ylamino)-ethyl]-1-[2-(N'',N''-dimethylaminomethyl)-ferrocenylmethyl]-3-p-methoxyphenyl-urea
Trypanosoma cruzi
-
-
0.0105
1-[2-(7-chloro-quinolin-4-ylamino)-ethyl]-1-[2-(N'',N''-dimethylaminomethyl)-ferrocenylmethyl]-3-[2,4-bis-(trifluoromethyl)-phenyl]-urea
Trypanosoma cruzi
-
-
0.0021
1-[2-(piperazin-1-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole
Trypanosoma cruzi
-
pH and temperature not specified in the publication
-
0.0029
1-[2-(piperidin-4-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole
Trypanosoma cruzi
-
pH and temperature not specified in the publication
-
0.0003
3,3'-[butane-1,4-diylbis[(3-aminopropyl)imino]]bis(N-[5-chloro-2-[(4-methoxyphenyl)sulfanyl]phenyl]propanamide)
Trypanosoma cruzi
-
IC50: 0.0003 mM
0.1
3-(methylsulfanyl)-5-phenyl-1,2,4-triazine
Trypanosoma cruzi
-
IC50 above 0.1 mM, in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.015
3-benzyl-1-[2-(7-chloro-quinolin-4-ylamino)-ethyl]-1-[2-(N'',N''-dimethylaminomethyl)-ferrocenylmethyl]urea
Trypanosoma cruzi
-
-
0.0032
3-Benzyl-1-[3-(7-chloro-quinolin-4-ylamino)-propyl]-1-[2-(N'',N''-dimethylaminomethyl)-ferrocenylmethyl]urea
Trypanosoma cruzi
-
-
0.0033
3-Benzyl-1-[4-(7-chloro-quinolin-4-ylamino)-butyl]-1-[2-(N'',N''-dimethylaminomethyl)-ferrocenylmethyl]urea
Trypanosoma cruzi
-
-
0.0024
3-Benzyl-1-[6-(7-chloro-quinolin-4-ylamino)-hexyl]-1-[2-(N'',N''-dimethylaminomethyl)-ferrocenylmethyl]urea
Trypanosoma cruzi
-
-
0.0065
3-Chloro-5-(3-(dimethylamino)propyl)-10,11-dihydro-5H-dibenz(b,f)azepine
Trypanosoma cruzi
-
IC50: 0.0065 mM
0.052
3-cyano-1-azabicyclo[2.2.2]oct-3-yl acetate
Trypanosoma cruzi
-
in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.027
3-methoxy-3'-(methylsulfanyl)-5,5'-bi-1,2,4-triazine
Trypanosoma cruzi
-
in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.017
4,6,8-trimethyl-N-(4,4,6-trimethyl-1,4-dihydropyrimidin-2-yl)quinazolin-2-amine
Trypanosoma cruzi
-
in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.1
5,6-dimethyl-2-[(4,6,8-trimethylquinazolin-2-yl)amino]pyrimidin-4-ol
Trypanosoma cruzi
-
IC50 above 0.1 mM, in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.0063
5-[2-(1-benzothiophen-5-yl)-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-3-yl]-1H-indole
Trypanosoma cruzi
-
pH and temperature not specified in the publication
-
0.0043
5-[2-phenyl-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-3-yl]-1H-indole
Trypanosoma cruzi
-
pH and temperature not specified in the publication
-
0.0048
5-[3-(1-benzothiophen-5-yl)-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole
Trypanosoma cruzi
-
pH and temperature not specified in the publication
-
0.0056
5-[3-phenyl-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole
Trypanosoma cruzi
-
pH and temperature not specified in the publication
-
0.004
5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole
Trypanosoma cruzi
-
pH and temperature not specified in the publication
-
0.028
7-ethoxy-4-methyl-N-(4,4,6-trimethyl-4,5-dihydropyrimidin-2-yl)quinazolin-2-amine
Trypanosoma cruzi
-
in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.032
7-ethyl-4-methyl-N-(4,4,6-trimethyl-4,5-dihydropyrimidin-2-yl)quinazolin-2-amine
Trypanosoma cruzi
-
in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.004
heptyl (2E)-2-[(2E)-3-(5-nitrofuran-2-yl)prop-2-en-1-ylidene]hydrazinecarboxylate
Trypanosoma cruzi
-
-
0.0036
hexyl (2E)-2-[(5-nitrofuran-2-yl)methylidene]hydrazinecarboxylate
Trypanosoma cruzi
-
-
0.0485
N,N'-(furan-2,5-diyldibenzene-4,1-diyl)diacetamide
Trypanosoma cruzi
-
IC50: 0.0485 mM, 54% inhibition at 0.02 mg/ml
0.1
N-(4,6-dimethylpyrimidin-2-yl)-4,5,7-trimethylquinazolin-2-amine
Trypanosoma cruzi
-
IC50 above 0.1 mM, in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.1
N-(4,6-dimethylpyrimidin-2-yl)-4,6-dimethylquinazolin-2-amine
Trypanosoma cruzi
-
IC50 above 0.1 mM, in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.0027
N-(7-Chloro-quinolin-4-yl)-N'-[2-(N'',N''-dimethyl-aminomethyl)ferrocenylmethyl]-butane-1,4-diamine
Trypanosoma cruzi
-
-
0.0476
N-(7-Chloro-quinolin-4-yl)-N'-[2-(N'',N''-dimethyl-aminomethyl)ferrocenylmethyl]-ethane-1,2-diamine
Trypanosoma cruzi
-
-
0.0021
N-(7-Chloro-quinolin-4-yl)-N'-[2-(N'',N''-dimethyl-aminomethyl)ferrocenylmethyl]-hexane-1,6-diamine
Trypanosoma cruzi
-
-
0.0068
N-(7-Chloro-quinolin-4-yl)-N'-[2-(N'',N''-dimethyl-aminomethyl)ferrocenylmethyl]-propane-1,3-diamine
Trypanosoma cruzi
-
-
0.033
N-[(4-chlorophenyl)(phenyl)methoxy]-8-methyl-8-azabicyclo[3.2.1]octan-3-imine
Trypanosoma cruzi
-
in 40 mM HEPES, 1 mM EDTA, 0.01% (v/v) bovine serum albumin, 0.05% (v/v) Tween 20, pH 7.5, 22°C
0.0368
N-[2-[(4-chlorophenyl)sulfanyl]phenyl]-2-phenylacetamide
Trypanosoma cruzi
-
IC50: 0.0368 mM
0.0445
N-[2-[(4-chlorophenyl)sulfanyl]phenyl]-4-nitrobenzamide
Trypanosoma cruzi
-
IC50: 0.0445 mM
0.0008
hypnophilin
Trypanosoma cruzi
-
using recombinant trypanothione reductase from Trypanosoma cruzi
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.18
-
recombinant mutant C58S: transhydrogenase activity between NADPH and thio-NADP+
0.21
-
recombinant mutant C53A: transhydrogenase activity between NADPH and thio-NADP+
0.44
-
recombinant mutant C53S: transhydrogenase activity between NADPH and thio-NADP+
6.49
-
recombinant wild-type: transhydrogenase activity between NADPH and thio-NADP+
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
7.5
-
glutathionylspermidine disulfide + NADPH, additional 2 minor optima at pH 7.0 and pH 8.0
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
trypanothione (N1,N8-bis(glutathyonil)spermidine) and trypanothione reductase, which are rather unique to trypanosomes and completely absent in mammalian cells
physiological function
the enzyme plays a central role in the metabolic pathway of the parasite
drug target
-
the enzyme is a promising targets for the development of drugs selective against parasites of the family of trypanosomatids
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). TYTR_TRYCR
492
0
53868
Swiss-Prot
Secretory Pathway (Reliability: 5), Secretory Pathway (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
molecular docking of inhibitor isopropyl 2-isobutyryl-3-trifluoromethylquinoxaline-7-carboxylate 1,4-di-N-oxide
purified recombinant enzyme, reduced by NADPH, inactivated by binding of quinacrine mustard, 13 mg/ml enzyme-inhibitor complex in Na+ malate, pH 6.0, with precipitant 20% w/v PEG 8000, X-ray diffraction structure determination and analysis at 2.7 A resolution
-
substrate binding and crystal structure in complex with trypanothione disulfide, molecular modeling with potential inhibitors
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C53A
-
site-directed mutagenesis, without catalytic active cysteine residue in the active center, no activity with trypanothione disulfide and NADPH, but showing transhydrogenase activity between NADPH and thio-NADP+
C53S
-
site-directed mutagenesis, without catalytic active cysteine residue in the active center, no activity with trypanothione disulfide and NADPH, but showing transhydrogenase activity between NADPH and thio-NADP+
C58S
-
site-directed mutagenesis, without catalytic active cysteine residue in the active center, no activity with trypanothione disulfide and NADPH, but showing transhydrogenase activity between NADPH and thio-NADP+
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
overexpression of wild-type and mutants C53S, C53A, C58S in Escherichia coli
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
pharmacology
medicine
good target for structure/function studies and trypanicidal inhibitor design
medicine
-
good target for structure/function studies and trypanicidal inhibitor design
medicine
-
potential target for drug design against trypanosomiasis
medicine
-
nitrofuran derivatives show antiparasitic effect on the trypanocidal drug design target trypanothione reductase
medicine
-
inhibition of the enzyme by naphthoquinone and nitrofuran derivatives abolish the cell penetration by the parasite trypomasstigotes, alternate approach to chemotherapy of trypanosomiasis and leishmaniasis, Chagas' disease
medicine
-
hypnophilin is good candidate for developing new drugs against Chagas disease
pharmacology
-
trypanothione reductase plays a central role in the trypanosomatid parasites defense against oxidative stress, trypanothione reductase is a promising target for antitrypanosomal drugs, binding affinity towards trypanothione reductase and glutathione reductase of nitrofuran derivatives is assessed by standard molecular docking procedures and both, energy and structural output analysis, nitrofuran ligands display a slight preference to bind the closely related human glutathione reductase, they should not be considered as drugs with selective inhibition of trypanothione reductase
pharmacology
-
trypanothione reductase plays a central role in the trypanosomatid parasites defense against oxidative stress, trypanothione reductase is a promising target for antitrypanosomal drugs, synthesis of dethiotrypanothione and related trypanothione analogues featuring ring-closing olefin metathesis macrocyclizations is described
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Krauth-Siegel, R.L.; Jockers-Scheruebl, M.C.; Becker, K.; Schirmer, R.H.
NADPH-dependent disulphide reductases
Biochem. Soc. Trans.
17
315-317
1989
Crithidia fasciculata, Trypanosoma congolense, Trypanosoma cruzi
Stoll, V.S.; Simpson, S.J.; Krauth-Siegel, R.L.; Walsh, C.T.; Pai, E.F.
Glutathione reductase turned into trypanothione reductase: structural analysis of an engineered change in substrate specificity
Biochemistry
36
6437-6447
1997
Homo sapiens, Trypanosoma cruzi
Gallwitz, H.; Bonse, S.; Martinez-Cruz, A.; Schlichting, I.; Schumacher, K.; Krauth-Siegel, R.L.
Ajoene is an inhibitor and subversive substrate of human glutathione reductase and Trypanosoma cruzi trypanothione reductase: crystallographic, kinetic, and spectroscopic studies
J. Med. Chem.
42
364-372
1999
Trypanosoma cruzi
Taylor, M.C.; Chapman, C.J.; Kelly, J.M.; Fairlamb, A.H.; Miles, M.A.
Cloning by expression of a cDNA corresponding to Leishmania donovani trypanothione reductase
Biochem. Soc. Trans.
17
579-580
1989
Crithidia fasciculata, Leishmania aethiopica, Leishmania donovani, Trypanosoma brucei, Trypanosoma congolense, Trypanosoma cruzi
-
Sullivan, F.X.; Shames, S.L.; Walsh, C.T.
Expression of Trypanosoma congolense trypanothione reductase in Escherichia coli: overproduction, purification, and characterization
Biochemistry
28
4986-4992
1989
Crithidia fasciculata, Trypanosoma congolense, Trypanosoma cruzi
Jockers-Scheruebl, M.C.; Schirmer, R.H.; Krauth-Siegel, R.L.
Trypanothione reductase from Trypanosoma cruzi. Catalytic properties of the enzyme and inhibition studies with trypanocidal compounds
Eur. J. Biochem.
180
267-272
1989
Trypanosoma cruzi
Henderson, G.B.; Ulrich, P.; Fairlamb, A.H.; Rosenberg, I.; Pereira, M.; Sela, M.; Cerami, A.
Subversive substrates for the enzyme trypanothione disulfide reductase: alternative approach to chemotherapy of Chagas disease
Proc. Natl. Acad. Sci. USA
85
5374-5378
1988
Crithidia fasciculata, Trypanosoma cruzi
Krauth-Siegel, R.L.; Enders, B.; Henderson, G.B.; Fairlamb, A.H.; Schirmer, R.H.
Trypanothione reductase from Trypanosoma cruzi. Purification and characterization of the crystalline enzyme
Eur. J. Biochem.
164
123-128
1987
Trypanosoma cruzi
Garrard, E.A.; Borman, E.C.; Cook, B.N.; Pike, E.J.; Alberg, D.G.
Inhibition of trypanothione reductase by substrate analogues
Org. Lett.
2
3639-3642
2000
Trypanosoma cruzi
Blumenstiel, K.; Schoneck, R.; Yardley, V.; Croft, S.L.; Krauth-Siegel, R.L.
Nitrofuran drugs as common subversive substrates of Trypanosoma cruzi lipoamide dehydrogenase and trypanothione reductase
Biochem. Pharmacol.
58
1791-1799
1999
Trypanosoma congolense, Trypanosoma cruzi
Bond, C.S.; Zhang, Y.; Berriman, M.; Cunningham, M.L.; Fairlamb, A.H.; Hunter, W.N.
Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors
Structure
7
81-89
1999
Trypanosoma cruzi
Davioud-Charvet, E.; Becker, K.; Landry, V.; Gromer, S.; Loge, C.; Sergheraert, C.
Synthesis of 5,5'-dithiobis(2-nitrobenzamides) as alternative substrates for trypanothione reductase and thioredoxin reductase: a microtiter colorimetric assay for inhibitor screening
Anal. Biochem.
268
1-8
1999
Trypanosoma cruzi
Kelly, J.M.; Taylor, M.C.; Smith, K.; Hunter, K.J.; Fairlamb, A.H.
Phenotype of recombinant Leishmania donovani and Trypanosoma cruzi which over-express trypanothione reductase. Sensitivity towards agents that are thought to induce oxidative stress
Eur. J. Biochem.
218
29-37
1993
Leishmania donovani, Trypanosoma cruzi
Borges, A.; Cunningham, M.L.; Tovar, J.; Fairlamb, A.H.
Site-directed mutagenesis of the redox-active cysteines of Trypanosoma cruzi trypanothione reductase
Eur. J. Biochem.
228
745-752
1995
Trypanosoma cruzi, Trypanosoma cruzi Silvio
Salmon-Chemin, L.; Buisine, E.; Yardley, V.; Kohler, S.; Debreu, M.A.; Landry, V.; Sergheraert, C.; Croft, S.L.; Krauth-Siegel, R.L.; Davioud-Charvet, E.
2- And 3-substituted 1,4-naphthoquinone derivatives as subversive substrates of trypanothione reductase and lipoamide dehydrogenase from Trypanosoma cruzi: Synthesis and correlation between redox cycling activities and in vitro cytotoxicity
J. Med. Chem.
44
548-565
2001
Leishmania donovani, Leishmania infantum, Trypanosoma brucei, Trypanosoma cruzi (P28593), Trypanosoma cruzi
Bonse, S.; Richards, J.M.; Ross, S.A.; Lowe, G.; Krauth-Siegel, R.L.
(2,2':6',2''-Terpyridine)platinum(II) complexes are irreversible inhibitors of Trypanosoma cruzi trypanothione reductase but not of human glutathione reductase
J. Med. Chem.
43
4812-4821
2000
Trypanosoma cruzi
Bonse, S.; Santelli-Rouvier, C.; Barbe, J.; Krauth-Siegel, R.L.
Inhibition of Trypanosoma cruzi trypanothione reductase by acridines: kinetic studies and structure-activity relationships
J. Med. Chem.
42
5448-5454
1999
Trypanosoma cruzi
Fournet, A.; Inchausti, A.; Yaluff, G.; Royas De Arias, A.; Guinaudeau, H.; Bruneton, J.; Breidenbach, M.A.; Karplus, P.A.; Faerman, C.H.
Trypanocidal bisbenzylisoquinoline alkaloids are inhibitors of trypanothione reductase
J. Enzyme Inhib.
13
1-9
1998
Trypanosoma cruzi
Bonnet, B.; Soullez, D.; Davioud-Charvet, E.; Landry, V.; Horvath, D.; Sergheraert, C.
New spermine and spermidine derivatives as potent inhibitors of Trypanosoma cruzi trypanothione reductase
Bioorg. Med. Chem.
5
1249-1256
1997
Trypanosoma cruzi
Hamilton, C.J.; Saravanamuthu, A.; Fairlamb, A.H.; Eggleston, I.M.
Benzofuranyl 3,5-bis-polyamine derivatives as time-dependent inhibitors of trypanothione reductase
Bioorg. Med. Chem.
11
3683-3693
2003
Trypanosoma cruzi
Saravanamuthu, A.; Vickers, T.J.; Bond, C.S.; Peterson, M.R.; Hunter, W.N.; Fairlamb, A.H.
Two interacting binding sites for quinacrine derivatives in the active site of trypanothione reductase: a template for drug design
J. Biol. Chem.
279
29493-29500
2004
no activity in Homo sapiens, Trypanosoma cruzi
Inhoff, O.; Richards, J.M.; Briet, J.W.; Lowe, G.; Krauth-Siegel, R.L.
Coupling of a competitive and an irreversible ligand generates mixed type inhibitors of Trypanosoma cruzi trypanothione reductase
J. Med. Chem.
45
4524-4530
2002
Trypanosoma cruzi
Dixon, M.J.; Maurer, R.I.; Biggi, C.; Oyarzabal, J.; Essex, J.W.; Bradley, M.
Mechanism and structure-activity relationships of norspermidine-based peptidic inhibitors of trypanothione reductase
Bioorg. Med. Chem.
13
4513-4526
2005
Trypanosoma cruzi
Meiering, S.; Inhoff, O.; Mies, J.; Vincek, A.; Garcia, G.; Kramer, B.; Dormeyer, M.; Krauth-Siegel, R.L.
Inhibitors of Trypanosoma cruzi trypanothione reductase revealed by virtual screening and parallel synthesis
J. Med. Chem.
48
4793-4802
2005
Trypanosoma cruzi
Lee, B.; Bauer, H.; Melchers, J.; Ruppert, T.; Rattray, L.; Yardley, V.; Davioud-Charvet, E.; Krauth-Siegel, R.L.
Irreversible inactivation of trypanothione reductase by unsaturated Mannich bases: a divinyl ketone as key intermediate
J. Med. Chem.
48
7400-7410
2005
Trypanosoma cruzi
Parveen, S.; Khan, M.O.; Austin, S.E.; Croft, S.L.; Yardley, V.; Rock, P.; Douglas, K.T.
Antitrypanosomal, antileishmanial, and antimalarial activities of quaternary arylalkylammonium 2-amino-4-chlorophenyl phenyl sulfides, a new class of trypanothione reductase inhibitor, and of N-acyl derivatives of 2-amino-4-chlorophenyl phenyl sulfide
J. Med. Chem.
48
8087-8097
2005
Trypanosoma cruzi
de Oliveira, R.B.; Vaz, A.B.; Alves, R.O.; Liarte, D.B.; Donnici, C.L.; Romanha, A.J.; Zani, C.L.
Arylfurans as potential Trypanosoma cruzi trypanothione reductase inhibitors
Mem. Inst. Oswaldo Cruz
101
169-173
2006
Trypanosoma cruzi
Blackie, M.A.; Saravanamuthu, A.; Fairlamb, A.H.; Chibale, K.
Inhibition of trypanothione reductase and glutathione reductase by ferrocenic 4-aminoquinoline ureas
ARKIVOC
2008
52-60
2008
Leishmania donovani, Trypanosoma brucei rhodesiense, Trypanosoma cruzi
-
Galarreta, B.C.; Sifuentes, R.; Carrillo, A.K.; Sanchez, L.; Amado, M.d.e.l.R.; Maruenda, H.
The use of natural product scaffolds as leads in the search for trypanothione reductase inhibitors
Bioorg. Med. Chem.
16
6689-6695
2008
Leishmania amazonensis, Trypanosoma cruzi
Cota, B.B.; Rosa, L.H.; Caligiorne, R.B.; Rabello, A.L.; Almeida Alves, T.M.; Rosa, C.A.; Zani, C.L.
Altenusin, a biphenyl isolated from the endophytic fungus Alternaria sp., inhibits trypanothione reductase from Trypanosoma cruzi
FEMS Microbiol. Lett.
285
177-182
2008
Leishmania amazonensis, Trypanosoma cruzi
Czechowicz, J.A.; Wilhelm, A.K.; Spalding, M.D.; Larson, A.M.; Engel, L.K.; Alberg, D.G.
The synthesis and inhibitory activity of dethiotrypanothione and analogues against trypanothione reductase
J. Org. Chem.
72
3689-3693
2007
Trypanosoma cruzi
Cota, B.B.; Rosa, L.H.; Fagundes, E.M.; Martins-Filho, O.A.; Correa-Oliveira, R.; Romanha, A.J.; Rosa, C.A.; Zani, C.L.
A potent trypanocidal component from the fungus Lentinus strigosus inhibits trypanothione reductase and modulates PBMC proliferation
Mem. Inst. Oswaldo Cruz
103
263-270
2008
Trypanosoma cruzi
Iribarne, F.; Gonzalez, M.; Cerecetto, H.; Aguilera, S.; Tapia, O.; Paulino, M.
Interaction energies of nitrofurans with trypanothione reductase and glutathione reductase studied by molecular docking
Theochem
818
7-22
2007
Trypanosoma cruzi
-
Cavalli, A.; Lizzi, F.; Bongarzone, S.; Brun, R.; Luise Krauth-Siegel, R.; Bolognesi, M.L.
Privileged structure-guided synthesis of quinazoline derivatives as inhibitors of trypanothione reductase
Bioorg. Med. Chem. Lett.
19
3031-3035
2009
Trypanosoma cruzi
Porcal, W.; Hernandez, P.; Boiani, L.; Boiani, M.; Ferreira, A.; Chidichimo, A.; Cazzulo, J.J.; Olea-Azar, C.; Gonzalez, M.; Cerecetto, H.
New trypanocidal hybrid compounds from the association of hydrazone moieties and benzofuroxan heterocycle
Bioorg. Med. Chem.
16
6995-7004
2008
Trypanosoma cruzi
Stump, B.; Eberle, C.; Schweizer, W.; Kaiser, M.; Brun, R.; Krauth-Siegel, R.; Lentz, D.; Diederich, F.
Pentafluorosulfanyl as a novel building block for enzyme inhibitors: Trypanothione reductase inhibition and antiprotozoal activities of diarylamines
ChemBioChem
10
79-83
2009
Trypanosoma cruzi (P28593)
Eberle, C.; Burkhard, J.A.; Stump, B.; Kaiser, M.; Brun, R.; Krauth-Siegel, R.L.; Diederich, F.
Synthesis, inhibition potency, binding mode, and antiprotozoal activities of fluorescent inhibitors of trypanothione reductase based on mepacrine-conjugated diaryl sulfide scaffolds
ChemMedChem
4
2034-2044
2009
Plasmodium falciparum, Trypanosoma brucei rhodesiense, Trypanosoma brucei rhodesiense STIB900, Trypanosoma cruzi (P28593), Trypanosoma cruzi, Trypanosoma cruzi Tulahuen C4 (P28593)
Perez-Pineiro, R.; Burgos, A.; Jones, D.C.; Andrew, L.C.; Rodriguez, H.; Suarez, M.; Fairlamb, A.H.; Wishart, D.S.
Development of a novel virtual screening cascade protocol to identify potential trypanothione reductase inhibitors
J. Med. Chem.
52
1670-1680
2009
Trypanosoma cruzi (P28593), Trypanosoma cruzi, Trypanosoma brucei (P39051), Trypanosoma brucei
da Rocha Pita, S.S.; Cirino, J.J.; de Alencastro, R.B.; Castro, H.C.; Rodrigues, C.R.; Albuquerque, M.G.
Molecular docking of a series of peptidomimetics in the trypanothione binding site of T. cruzi trypanothione reductase
J. Mol. Graph. Model.
28
330-335
2009
Trypanosoma cruzi (P28593), Trypanosoma cruzi
Iribarne, F.; Paulino, M.; Aguilera, S.; Tapia, O.
Assaying phenothiazine derivatives as trypanothione reductase and glutathione reductase inhibitors by theoretical docking and Molecular Dynamics studies
J. Mol. Graph. Model.
28
371-381
2009
Trypanosoma cruzi (P28593), Trypanosoma cruzi
Holloway, G.A.; Charman, W.N.; Fairlamb, A.H.; Brun, R.; Kaiser, M.; Kostewicz, E.; Novello, P.M.; Parisot, J.P.; Richardson, J.; Street, I.P.; Watson, K.G.; Baell, J.B.
Trypanothione reductase high-throughput screening campaign identifies novel classes of inhibitors with antiparasitic activity
Antimicrob. Agents Chemother.
53
2824-2833
2009
Trypanosoma cruzi, Trypanosoma cruzi Silvio X10/1
Eberle, C.; Lauber, B.S.; Fankhauser, D.; Kaiser, M.; Brun, R.; Krauth-Siegel, R.L.; Diederich, F.
Improved inhibitors of trypanothione reductase by combination of motifs: synthesis, inhibitory potency, binding mode, and antiprotozoal activities
ChemMedChem
6
292-301
2011
Leishmania donovani, Plasmodium falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi (P28593)
Rodrigues, R.F.; Castro-Pinto, D.; Echevarria, A.; dos Reis, C.M.; Del Cistia, C.N.; SantAnna, C.M.; Teixeira, F.; Castro, H.; Canto-Cavalheiro, M.; Leon, L.L.; Tomas, A.
Investigation of trypanothione reductase inhibitory activity by 1,3,4-thiadiazolium-2-aminide derivatives and molecular docking studies
Bioorg. Med. Chem.
20
1760-1766
2012
Leishmania amazonensis, Leishmania amazonensis MHOM/BR/LTB0016, Leishmania braziliensis, Leishmania braziliensis MCAN/BR/98/R619, Leishmania infantum, Leishmania infantum MHOM/MA67ITMAP263, Trypanosoma cruzi, Trypanosoma cruzi Y
Lazarin-Bidoia, D.; Desoti, V.C.; Ueda-Nakamura, T.; Dias Filho, B.P.; Nakamura, C.V.; Silva, S.O.
Further evidence of the trypanocidal action of eupomatenoid-5: confirmation of involvement of reactive oxygen species and mitochondria owing to a reduction in trypanothione reductase activity
Free Radic. Biol. Med.
60
17-28
2013
Trypanosoma cruzi
Arias, D.G.; Herrera, F.E.; Garay, A.S.; Rodrigues, D.; Forastieri, P.S.; Luna, L.E.; Buergi, M.D.; Prieto, C.; Iglesias, A.A.; Cravero, R.M.; Guerrero, S.A.
Rational design of nitrofuran derivatives Synthesis and valuation as inhibitors of Trypanosoma cruzi trypanothione reductase
Eur. J. Med. Chem.
125
1088-1097
2017
Trypanosoma cruzi (V5AJG2), Trypanosoma cruzi, Trypanosoma cruzi Dm28c (V5AJG2)
Chacon-Vargas, K.F.; Nogueda-Torres, B.; Sanchez-Torres, L.E.; Suarez-Contreras, E.; Villalobos-Rocha, J.C.; Torres-Martinez, Y.; Lara-Ramirez, E.E.; Fiorani, G.; Krauth-Siegel, R.L.; Bolognesi, M.L.; Monge, A.; Rivera, G.
Trypanocidal activity of quinoxaline 1,4 di-N-oxide derivatives as trypanothione reductase inhibitors
Molecules
22
220
2017
Trypanosoma cruzi (P28593)
Argueelles, A.J.; Cordell, G.A.; Maruenda, H.
Molecular docking and binding mode analysis of plant alkaloids as in vitro and in silico inhibitors of trypanothione reductase from Trypanosoma cruzi
Nat. Prod. Commun.
11
57-62
2016
Trypanosoma cruzi
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
ChemMedChem
13
957-967
2018
Trypanosoma cruzi, Trypanosoma brucei brucei (Q389T8), Trypanosoma brucei brucei 927/4 GUTat10.1 (Q389T8)
Vazquez, K.; Paulino, M.; Salas, C.O.; Zarate-Ramos, J.J.; Vera, B.; Rivera, G.
Trypanothione reductase a target for the development of anti-Trypanosoma cruzi drugs
Mini Rev. Med. Chem.
17
939-946
2017
Trypanosoma cruzi (P28593), Trypanosoma cruzi
Rodriguez-Becerra, J.; Caceres-Jensen, L.; Hernandez-Ramos, J.; Barrientos, L.
Identification of potential trypanothione reductase inhibitors among commercially available beta-carboline derivatives using chemical space, lead-like and drug-like filters, pharmacophore models and molecular docking
Mol. Divers.
21
697-711
2017
Trypanosoma cruzi (P28593), Trypanosoma cruzi
Lenz, M.; Krauth-Siegel, R.L.; Schmidt, T.J.
Natural sesquiterpene lactones of the 4,15-iso-atriplicolide type are inhibitors of trypanothione reductase
Molecules
24
3737
2019
Trypanosoma brucei rhodesiense, Trypanosoma cruzi (P28593)
Coro-Bermello, J.; Lopez-Rodriguez, E.; Alfonso-Ramos, J.; Alonso, D.; Ojeda-Carralero, G.; Prado, G.; Moreno-Castillo, E.
Identification of novel thiadiazin derivatives as potentially selective inhibitors towards trypanothione reductase from Trypanosoma cruzi by molecular docking using the numerical index poses ratio Pr and the binding mode analysis
SN Appl. Sci.
3
376
2021
Trypanosoma cruzi (P28593)
-
EXTERNAL LINKS (specific for EC-Number 1.8.1.12)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
