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Information on EC 1.3.1.9 - enoyl-[acyl-carrier-protein] reductase (NADH) and Organism(s) Mycobacterium tuberculosis and UniProt Accession P9WGR1
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1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH)IUBMB Comments
The enzyme catalyses an essential step in fatty acid biosynthesis, the reduction of the 2,3-double bond in enoyl-acyl-[acyl-carrier-protein] derivatives of the elongating fatty acid moiety. The enzyme from the bacterium Escherichia coli accepts substrates with carbon chain length from 4 to 18 . The FAS-I enzyme from the bacterium Mycobacterium tuberculosis prefers substrates with carbon chain length from 12 to 24 carbons.
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Word Map
- 1.3.1.9
- tuberculosis
- mycobacterium
- triclosan
- falciparum
- plasmodium
- isoniazid
- medicine
-
antitubercular
-
mycolic
-
antimycobacterial
- diazaborine
-
triclosan-resistant
-
pyrrolyl
-
comsia
-
surflex-docking
-
inh-resistant
- drug development
- analysis
- pharmacology
The taxonomic range for the selected organisms is: Mycobacterium tuberculosis
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
pfenr, enoyl-acyl carrier protein, enoyl acyl carrier protein reductase, mtinha, enoyl acp reductase, enoyl-reductase, nadh-dependent enoyl-acp reductase, fabi1, fabi2, nadh-dependent enoyl-acyl carrier protein reductase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
enoyl acyl carrier protein reductase
-
InhA
-
cold-shock induced protein 15
-
-
-
-
CSI15
-
-
-
-
enoyl-ACP reductase
InhA
-
-
NADH-dependent enoyl-ACP reductase
-
-
-
-
NADH-enoyl acyl carrier protein reductase
-
-
-
-
NADH-specific enoyl-ACP reductase
-
-
-
-
reductase, enoyl-[acyl carrier protein]
-
-
-
-
VEG241
-
-
-
-
vegetative protein 241
-
-
-
-
enoyl-ACP reductase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
reduction
redox reaction
-
-
-
-
oxidation
reduction
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
acyl-[acyl-carrier protein]:NAD+ oxidoreductase
The enzyme catalyses an essential step in fatty acid biosynthesis, the reduction of the 2,3-double bond in enoyl-acyl-[acyl-carrier-protein] derivatives of the elongating fatty acid moiety. The enzyme from the bacterium Escherichia coli accepts substrates with carbon chain length from 4 to 18 [3]. The FAS-I enzyme from the bacterium Mycobacterium tuberculosis prefers substrates with carbon chain length from 12 to 24 carbons.
CAS REGISTRY NUMBER
COMMENTARY
37251-08-4
-
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
a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
an acyl-[acyl-carrier protein] + NAD+
-
-
-
?
acyl-[acyl-carrier protein] + NAD+
trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
an acyl-[acyl-carrier protein] + NAD+
a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
-
-
-
?
trans-2-decenoyl-CoA + NADH + H+
decanoyl-CoA + NAD+
-
-
-
?
trans-2-enoyl-[acyl-carrier protein] + NADH
acyl-[acyl-carrier protein] + NAD+
-
-
-
?
trans-2-hexadecenoyl-CoA + NADH + H+
hexadecanoyl-CoA + NAD+
-
-
-
?
trans-2-octenoyl-CoA + NADH + H+
octanoyl-CoA + NAD+
-
-
-
?
trans-DELTA2-enolyl-[acyl-carrier protein] + NADH + H+
acyl-[acyl-carrier protein] + NAD+
-
-
-
?
trans-DELTA2-enolyl-[acyl-carrier protein] + NADH + H+
enolyl-[acyl-carrier protein] + NAD+
-
-
-
?
trans-DELTA2-enoyl-[acyl-carrier protein] + NADH + H+
enoyl-[acyl-carrier protein] + NAD+
-
-
-
?
2-trans-dodecenoyl-CoA + NADH + H+
dodecanoyl-CoA + NAD+
-
-
-
-
?
a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
an acyl-[acyl-carrier protein] + NAD+
-
-
-
-
?
acyl-[acyl-carrier protein] + NAD+
trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
-
-
-
-
?
an acyl-[acyl-carrier protein] + NAD+
a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
trans-2,3-dehydracyl-[acyl-carrier protein] + NADH + H+
acyl-[acyl-carrier protein] + NAD+
-
-
-
-
?
additional information
?
-
activity detection using trans-2-dodecenyl-CoA and NADH as substrate and cofactor
-
-
?
acyl-[acyl-carrier protein] + NAD+
trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
-
-
-
?
acyl-[acyl-carrier protein] + NAD+
trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
-
-
-
-
?
trans-2-dodecenoyl-CoA + NADH + H+
dodecanoyl-CoA + NAD+
-
-
-
?
trans-2-dodecenoyl-CoA + NADH + H+
dodecanoyl-CoA + NAD+
-
-
-
-
?
trans-2-dodecenoyl-CoA + NADH + H+
dodecanoyl-CoA + NAD+
-
-
-
?
trans-2-dodecenoyl-CoA + NADH + H+
dodecanoyl-CoA + NAD+
-
-
-
-
?
trans-2-dodecenoyl-CoA + NADH + H+
dodecanoyl-CoA + NAD+
-
-
-
?
an acyl-[acyl-carrier protein] + NAD+
a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
-
-
-
-
?
an acyl-[acyl-carrier protein] + NAD+
a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
-
-
-
-
r
trans-2-dodecenoyl-CoA + NADH + H+
dodecanoyl-CoA + NAD+
-
-
-
-
?
trans-2-dodecenoyl-CoA + NADH + H+
dodecanoyl-CoA + NAD+
-
pre-steady state kinetics and equilibrium data of 2-trans-dodecenoyl-CoA substrate binding to InhA. The results indicate both positive homotropic cooperativity upon substrate binding to InhA, and a bimolecular association process followed by a slow isomerization of the enzyme-substrate binary complex
-
-
?
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
a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
an acyl-[acyl-carrier protein] + NAD+
-
-
-
?
acyl-[acyl-carrier protein] + NAD+
trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
-
-
-
?
an acyl-[acyl-carrier protein] + NAD+
a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
-
-
-
?
trans-2-enoyl-[acyl-carrier protein] + NADH
acyl-[acyl-carrier protein] + NAD+
-
-
-
?
trans-DELTA2-enolyl-[acyl-carrier protein] + NADH + H+
acyl-[acyl-carrier protein] + NAD+
-
-
-
?
trans-DELTA2-enolyl-[acyl-carrier protein] + NADH + H+
enolyl-[acyl-carrier protein] + NAD+
-
-
-
?
trans-DELTA2-enoyl-[acyl-carrier protein] + NADH + H+
enoyl-[acyl-carrier protein] + NAD+
-
-
-
?
a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
an acyl-[acyl-carrier protein] + NAD+
-
-
-
-
?
acyl-[acyl-carrier protein] + NAD+
trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
-
-
-
-
?
an acyl-[acyl-carrier protein] + NAD+
a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
trans-2,3-dehydracyl-[acyl-carrier protein] + NADH + H+
acyl-[acyl-carrier protein] + NAD+
-
-
-
-
?
an acyl-[acyl-carrier protein] + NAD+
a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
-
-
-
-
?
an acyl-[acyl-carrier protein] + NAD+
a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
-
-
-
-
r
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADH
-
-
655226, 672640, 673230, 675385, 689435, 697217, 740323, 740846, 741435, 747579, 764624, 764632, 765866
NADH
although very flexible, in the wild-type enzyme/NADH complex, the NADH molecule keeps its extended conformation firmly bound to the binding site of the enzyme
NADH
while NADH binding to wild-type InhA is hyperbolic, the InhA mutants bind the cofactor with positive cooperativity, suggesting that the mutations permit access to a second conformational state of the protein
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1H-indol-5-yl)[4-[(4-methylphenyl)(phenyl)methyl]piperazin-1-yl]methanone
0.015 mM, 74% inhibition
(2E)-1-[4-(1H-pyrrol-1-yl)phenyl]-3-[4-(trifluoromethyl)phenyl]prop-2-en-1-one
-
-
(2E)-3-(4-methoxyphenyl)-1-[4-(1H-pyrrol-1-yl)phenyl]prop-2-en-1-one
-
-
(2E)-3-(4-methylphenyl)-1-[4-(1H-pyrrol-1-yl)phenyl]prop-2-en-1-one
-
-
(2E)-3-(6-fluorocyclohexa-1,5-dien-1-yl)-1-[4-(1H-pyrrol-1-yl)phenyl]prop-2-en-1-one
-
-
(2E)-3-[(4Z)-4-ethylidenecyclohexa-1,5-dien-1-yl]-1-[4-(1H-pyrrol-1-yl)phenyl]prop-2-en-1-one
-
-
(4-(9H-fluoren-9-yl) piperazin-1-yl)-(4-methylbenzyl)-methanone
0.015 mM, 99% inhibition
(4-(9H-fluoren-9-yl)piperazin-1-yl) (2,5-difluorophenyl)methanone
uncompetitive versus NADH, noncompetitive versus trans-2-dodecenoyl-CoA
(4-(9H-fluoren-9-yl)piperazin-1-yl) (2-fluorophenyl)methanone
uncompetitive versus NADH, noncompetitive versus trans-2-dodecenoyl-CoA
(4-(9H-fluoren-9-yl)piperazin-1-yl) (3-fluorophenyl)methanone
uncompetitive versus NADH, competitive versus trans-2-dodecenoyl-CoA
(4-(9H-Fluoren-9-yl)piperazin-1-yl) (3-tolyl)methanone
uncompetitive versus NADH, noncompetitive versus trans-2-dodecenoyl-CoA
(4-(9H-fluoren-9-yl)piperazin-1-yl) (4-chlorophenyl)methanone
uncompetitive versus NADH, noncompetitive versus trans-2-dodecenoyl-CoA
(4-(9H-fluoren-9-yl)piperazin-1-yl) (4-fluorophenyl)methanone
uncompetitive versus NADH, competitive versus trans-2-dodecenoyl-CoA
(4-(9H-fluoren-9-yl)piperazin-1-yl) (4-methoxyphenyl)methanone
uncompetitive versus NADH, noncompetitive versus trans-2-dodecenoyl-CoA
(4-(9H-fluoren-9-yl)piperazin-1-yl) (4-tolyl)methanone
uncompetitive versus NADH, competitive versus trans-2-dodecenoyl-CoA
(4-(9H-fluoren-9-yl)piperazin-1-yl) (phenyl)methanone
uncompetitive versus NADH, noncompetitive versus trans-2-dodecenoyl-CoA
(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)-(1H-indole-5-carbonyl)-methanone
0.015 mM, 84% inhibition
(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)-(4-methylbenzyl)-methanone
0.015 mM, 83% inhibition
(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)-benzyl-methanone
0.015 mM, 81% inhibition
(4-methylphenyl)[4-[(4-methylphenyl)(phenyl)methyl]piperazin-1-yl]methanone
0.015 mM, 77% inhibition
1-(2,4-dichlorophenyl)-3-(3-methylpyridin-2-yl)thiourea
47% inhibition at 0.05 mM
-
1-(2-(4-(1H-pyrrol-1-yl)phenoxy)acetyl)-1,2-diazepane-3,7-dione
18% inhibition at 0.05 mM
-
1-(2-(4-(1H-pyrrol-1-yl)phenoxy)acetyl)-1,2-dihydropyridazine-3,6-dione
less than 5% inhibition at 0.05 mM
-
1-(2-(4-(1H-pyrrol-1-yl)phenoxy)acetyl)-4-methyl-1,2-dihydropyridazine-3,6-dione
42% inhibition at 0.05 mM
-
1-(2-(4-(1H-pyrrol-1-yl)phenoxy)acetyl)-4-methylenetetrahydropyridazine-3,6-dione
50% inhibition at 0.05 mM
-
1-(2-(4-(1H-pyrrol-1-yl)phenoxy)acetyl)tetrahydropyridazine-3,6-dione
32% inhibition at 0.05 mM
-
1-(2-bromobenzyl)-3-(4-nitrophenyl)thiourea
78% inhibition at 0.05 mM
-
1-(2-bromobenzyl)-3-phenylthiourea
23% inhibition at 0.05 mM
-
1-(2-chlorobenzyl)-3-(4-nitrophenyl)thiourea
72% inhibition at 0.05 mM
-
1-(2-chlorobenzyl)-3-phenylthiourea
31% inhibition at 0.05 mM
-
1-(2-chlorobenzyl)-3-phenylurea
14% inhibition at 0.05 mM
-
1-(3,5-bis(trifluoromethyl)phenyl)-3-(3-methylpyridin-2-yl)thiourea
22% inhibition at 0.05 mM
-
1-(3-chlorocyclohexyl)-4-[(2-fluorophenyl)carbonyl]piperazine
-
1-(3-chlorocyclohexyl)-4-[(3,4-dichlorophenyl)carbonyl]piperazine
-
1-(3-chlorocyclohexyl)-4-[(3,4-dimethylphenyl)carbonyl]piperazine
-
1-(3-chlorocyclohexyl)-4-[(3-chlorophenyl)carbonyl]piperazine
-
1-(3-chlorocyclohexyl)-4-[(3-methylphenyl)carbonyl]piperazine
-
1-(3-chlorocyclohexyl)-4-[(4-fluorophenyl)carbonyl]piperazine
-
1-(3-chlorocyclohexyl)-4-[(4-methylphenyl)carbonyl]piperazine
-
1-(3-methylpyridin-2-yl)-3-(2-(trifluoromethyl)phenyl)thiourea
32% inhibition at 0.05 mM
-
1-(3-methylpyridin-2-yl)-3-(4-tolyl)thiourea
23% inhibition at 0.05 mM
-
1-(3-methylpyridin-2-yl)-3-(naphthalen-2-yl)thiourea
38% inhibition at 0.05 mM
-
1-(3-methylpyridin-2-yl)-3-phenylthiourea
35% inhibition at 0.05 mM
1-(4-(1H-pyrrol-1-yl)benzoyl)-1,2-diazepane-3,7-dione
27% inhibition at 0.05 mM
-
1-(4-(2,5-dimethyl-1H-pyrrol-1-yl)benzoyl)-1,2-diazepane-3,7-dione
13% inhibition at 0.05 mM
-
1-(4-bromophenyl)-3-(3-methylpyridin-2-yl)thiourea
25% inhibition at 0.05 mM
-
1-(4-fluorophenyl)-3-(3-methylpyridin-2-yl)thiourea
17% inhibition at 0.05 mM
-
1-(4-iodophenyl)-3-(3-methylpyridin-2-yl)thiourea
8% inhibition at 0.05 mM
-
1-(4-methoxyphenyl)-3-(3-methylpyridin-2-yl)thiourea
20% inhibition at 0.05 mM
-
1-(9H-fluoren-9-yl)-4-[(4-methylphenyl)carbonyl]piperazine
-
1-([1,5-bis(4-chlorophenyl)-2-methyl-1H-pyrrol-3-yl]methyl)-4-methylpiperazine
i.e. BM-212
-
1-bicyclo[2.2.1]hept-2-yl-N-biphenyl-3-yl-5-oxopyrrolidine-3-carboxamide
-
1-cycloheptyl-N-(2'-hydroxy-1,1':3',1''-terphenyl-4'-yl)-5-oxopyrrolidine-3-carboxamide
-
1-cyclohexyl-4-(2,3-dihydro-1H-indol-1-ylcarbonyl)pyrrolidin-2-one
-
1-cyclohexyl-4-([4-[(4-fluorophenyl)(phenyl)methyl]piperazin-1-yl]carbonyl)pyrrolidin-2-one
-
1-cyclohexyl-4-([4-[(4-methylphenyl)(phenyl)methyl]piperazin-1-yl]carbonyl)pyrrolidin-2-one
-
1-cyclohexyl-5-oxo-N-[3-(trifluoromethyl)phenyl]pyrrolidine-3-carboxamide
-
1-cyclohexyl-N-(2,4-dichlorophenyl)-5-oxopyrrolidine-3-carboxamide
-
1-cyclohexyl-N-(2,5-dichlorophenyl)-5-oxopyrrolidine-3-carboxamide
-
1-cyclohexyl-N-(2,5-dimethylphenyl)-5-oxopyrrolidine-3-carboxamide
-
1-cyclohexyl-N-(2-methyl-4-nitrophenyl)-5-oxopyrrolidine-3-carboxamide
-
1-cyclohexyl-N-(3,5-dichlorophenyl)-5-oxopyrrolidine-3-carboxamide
-
1-cyclohexyl-N-(3,5-difluorophenyl)-5-oxopyrrolidine-3-carboxamide
-
1-cyclohexyl-N-(3,5-dimethylphenyl)-5-oxopyrrolidine-3-carboxamide
-
1-cyclohexyl-N-(3,5-diphenyl-4-hydroxyl)phenyl-5-oxopyrrolidine-3-carboxamide
best inhibitor of the sreening with an IC50: 62 nanoM
1-cyclohexyl-N-(3-methylphenyl)-5-oxopyrrolidine-3-carboxamide
-
1-cyclohexyl-N-(3-nitrophenyl)-5-oxopyrrolidine-3-carboxamide
-
1-cyclohexyl-N-(4-iodophenyl)-5-oxopyrrolidine-3-carboxamide
-
1-cyclohexyl-N-(9-ethyl-9H-carbazol-2-yl)-5-oxopyrrolidine-3-carboxamide
-
1-cyclohexyl-N-9H-fluoren-4-yl-5-oxopyrrolidine-3-carboxamide
-
1-cyclohexyl-N-[(2'-hydroxy-1,1':3',1''-terphenyl-5'-yl)methyl]-5-oxopyrrolidine-3-carboxamide
-
1-cyclohexyl-N-[3-(1-methylethyl)phenyl]-5-oxopyrrolidine-3-carboxamide
-
1-cyclohexyl-N-[3-methoxy-5-(trifluoromethyl)phenyl]-5-oxopyrrolidine-3-carboxamide
-
1-cyclooctyl-N-(2'-hydroxy-1,1':3',1''-terphenyl-4'-yl)-5-oxopyrrolidine-3-carboxamide
-
1-[(3,4-dimethylphenyl)carbonyl]-4-[3-(trifluoromethyl)cyclohexyl]piperazine
-
1-[(3-chlorophenyl)carbonyl]-4-(cyclohexylmethyl)piperidine
-
1-[(3-methylphenyl)carbonyl]-4-(4-nitrocyclohexyl)piperazine
-
1-[(4-methylphenyl)carbonyl]-4-[3-(trifluoromethyl)cyclohexyl]piperazine
-
1-[9-[4-(1H-indol-5-ylcarbonyl)piperazin-1-yl]-9H-fluoren-1-yl]ethanone
-
1-[bis(4-fluorophenyl)methyl]-4-(phenylcarbonyl)piperazine
-
1-[bis(4-fluorophenyl)methyl]-4-[(4-methylphenyl)carbonyl]piperazine
-
2,13-dioxapentacyclo[18.2.2.23,6.29,12.214,17]triaconta-1(22),3,5,9,11,14,16,20,23,25,27,29-dodecaene-4,11-diol
52% inhibition at 0.05 mM
-
2,13-dioxapentacyclo[18.2.2.23,6.29,12.214,17]triaconta-1(22),3,5,9,11,14,16,20,23,25,27,29-dodecaene-4,15-diol
93% inhibition at 0.05 mM
-
2-(2-(4-(1H-pyrrol-1-yl)phenoxy)acetyl)-2,3-dihydrophthalazine-1,4-dione
63% inhibition at 0.05 mM
-
2-(2-(4-(1H-pyrrol-1-yl)phenoxy)acetyl)-5,6,7,8-tetrabromo-2,3-dihydrophthalazine-1,4-dione
11% inhibition at 0.05 mM
-
2-(2-(4-(1H-pyrrol-1-yl)phenoxy)acetyl)-5,6,7,8-tetrachloro-2,3-dihydrophthalazine-1,4-dione
12% inhibition at 0.05 mM
-
2-(2-(4-(1H-pyrrol-1-yl)phenoxy)acetyl)octahydrophthalazine-1,4-dione
less than 5% inhibition at 0.05 mM
-
2-(2-chloro-4-fluorophenyl)-N-(4-((3,5-dimethyl-1H-pyrazol-1-yl)-methyl)phenyl)acetamide
-
2-(2-methyl-4-oxoquinazolin-3(4H)-yl)-N-(5-nitrothiazol-2-yl)acetamide
-
2-(2-methyl-4-oxoquinazolin-3(4H)-yl)-N-(6-nitrobenzo[d]thiazol-2-yl)acetamide
-
2-(2-methyl-4-oxoquinazolin-3(4H)-yl)-N-(thiophen-2-ylmethyl)acetamide
-
2-(4-(1H-pyrrol-1-yl)benzoyl)-5,6,7,8-tetrabromo-2,3-dihydrophthalazine-1,4-dione
72% inhibition at 0.05 mM
-
2-(4-(1H-pyrrol-1-yl)benzoyl)-5,6,7,8-tetrachloro-2,3-dihydrophthalazine-1,4-dione
64% inhibition at 0.05 mM
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(1-(4-bromophenyl)ethylidene)acetohydrazide
27% inhibition at 0.05 mM
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(1-(4-chlorophenyl)ethylidene)acetohydrazide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(1-(4-hydroxyphenyl)ethylidene)acetohydrazide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(1-(4-nitrophenyl)ethylidene)acetohydrazide
51% inhibition at 0.05 mM
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(1-phenylethylidene)acetohydrazide
34% inhibition at 0.05 mM
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(2,3-dichlorobenzylidene)acetohydrazide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(2,4-dichlorobenzylidene)acetohydrazide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(2,4-dimethoxybenzylidene)acetohydrazide
37% inhibition at 0.05 mM
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(2,6-dichlorobenzylidene)acetohydrazide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(2-chlorobenzylidene)acetohydrazide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(2-nitrobenzylidene)acetohydrazide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(3,4-dichlorobenzylidene)acetohydrazide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(3-bromobenzylidene)acetohydrazide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(3-ethoxy-4-hydroxybenzylidene)acetohydrazide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(3-hydroxybenzylidene)acetohydrazide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(3-methoxybenzylidene)acetohydrazide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(3-phenoxybenzylidene)acetohydrazide
15% inhibition at 0.05 mM
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(4-chlorobenzylidene)acetohydrazide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(4-fluorobenzylidene)acetohydrazide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(4-hydroxy-3-methoxybenzylideneacetohydrazide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(4-hydroxybenzylidene)acetohydrazide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(4-isopropylbenzylidene)acetohydrazide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(4-methoxybenzylidene)acetohydrazide
21% inhibition at 0.05 mM
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-(4-methylbenzylidene)acetohydrazide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N'-benzylideneacetohydrazide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N-(1,3-dioxoisoindolin-2-yl)acetamide
25% inhibition at 0.05 mM
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N-(1,3-dioxooctahydro-2H-isoindol-2-yl)acetamide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N-(2,5-dioxo-2,5-dihydro-1Hpyrrol-1-yl)acetamide
10% inhibition at 0.05 mM
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N-(2,5-dioxopyrrolidin-1-yl)acetamide
less than 5% inhibition at 0.05 mM
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N-(2,6-dioxopiperidin-1-yl)acetamide
20% inhibition at 0.05 mM
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N-(3-methyl-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetamide
10% inhibition at 0.05 mM
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N-(3-methylene-2,5-dioxopyrrolidin-1-yl)acetamide
21% inhibition at 0.05 mM
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N-(4,5,6,7-tetrabromo-1,3-dioxoisoindolin-2-yl)acetamide
-
-
2-(4-(1H-pyrrol-1-yl)phenoxy)-N-(4,5,6,7-tetrachloro-1,3-dioxoisoindolin-2-yl)acetamide
-
-
2-(4-(2,5-dimethyl-1H-pyrrol-1-yl)benzoyl)-5,6,7,8-tetrabromo-2,3-dihydrophthalazine-1,4-dione
75% inhibition at 0.05 mM
-
2-(4-(2,5-dimethyl-1H-pyrrol-1-yl)benzoyl)-5,6,7,8-tetrachloro-2,3-dihydrophthalazine-1,4-dione
76% inhibition at 0.05 mM
-
2-(4-chlorophenoxy)-5-[4-(1H-1,2,3-triazol-1-yl)butyl]phenol
-
-
2-(4-oxoquinazolin-3(4H)-yl)-N-(thiophen-2-ylmethyl)acetamide
-
2-(6-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)-N-(2-chloro-5-(trifluoromethyl)phenyl)acetamide
-
2-(6-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)-N-(5-nitrothiazol-2-yl)acetamide
-
2-(6-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)-N-(6-nitrobenzo[d]thiazol-2-yl)acetamide
-
2-(6-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)-N-(furan-2-ylmethyl)acetamide
-
2-(6-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)-N-(thiophen-2-ylmethyl)acetamide
-
2-(6-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)-N-[(furan-2-yl)methyl]acetamide
78.12% inhibition at 0.01 mM
-
2-(6-chloro-4-oxoquinazolin-3(4H)-yl)-N-(2-chloro-5-(trifluoromethyl)phenyl)acetamide
-
2-(6-chloro-4-oxoquinazolin-3(4H)-yl)-N-(5-nitrothiazol-2-yl)acetamide
-
2-(6-chloro-4-oxoquinazolin-3(4H)-yl)-N-(6-nitrobenzo[d]thiazol-2-yl)acetamide
-
2-(6-chloro-4-oxoquinazolin-3(4H)-yl)-N-(furan-2-ylmethyl)acetamide
-
2-(6-chloro-4-oxoquinazolin-3(4H)-yl)-N-(thiophen-2-ylmethyl)acetamide
-
2-(6-chloro-4-oxoquinazolin-3(4H)-yl)-N-[2-chloro-5-(trifluoromethyl)phenyl]acetamide
80.12% inhibition at 0.01 mM
-
2-(ethanesulfonyl)-6-[2-[(E)-(hydroxyimino)methyl]-4-(trifluoromethyl)phenoxy]-2,3,1-benzodiazaborinin-1(2H)-ol
-
2-(ethanesulfonyl)-7-[2-[(Z)-(hydroxyimino)methyl]-4-(trifluoromethyl)phenoxy]-2,3,1-benzodiazaborinin-1(2H)-ol
diazaborine, in vitro bactericidal activity against replicating bacteria active against several drug-resistant clinical isolates. AN12855 binds to and inhibits the substrate-binding site of InhA in a cofactor-independent manner. It shows good drug exposure after i.v. and oral delivery, with 53% oral bioavailability. Delivered orally, AN12855 exhibits dose-dependent efficacy in both an acute and chronic murine model of tuberculosis infection. AN12855 is a promising candidate for the development of new antitubercular agents
3-[(2E)-2-benzylidenehydrazinyl]-N-(2,4-dichlorophenyl)-1,2,4-thiadiazol-5-amine
-
-
3-[(2E)-2-benzylidenehydrazinyl]-N-(4-bromophenyl)-1,2,4-thiadiazol-5-amine
-
-
3-[(2E)-2-benzylidenehydrazinyl]-N-(4-methoxyphenyl)-1,2,4-thiadiazol-5-amine
-
-
3-[(2E)-2-[(4-methylphenyl)methylidene]hydrazinyl]-N-phenyl-1,2,4-thiadiazol-5-amine
-
-
4-(cyclohexylmethyl)-1-[(2-fluorophenyl)carbonyl]piperidine
-
4-(cyclohexylmethyl)-1-[(3-methylphenyl)carbonyl]piperidine
-
4-(cyclohexylmethyl)-1-[(4-methylphenyl)carbonyl]piperidine
-
4-([4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl]carbonyl)-1-cyclohexylpyrrolidin-2-one
-
4-([4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]carbonyl)-1-cyclohexylpyrrolidin-2-one
-
4-phenoxybenzamide adenine dinucleotide
NAD analogue which mimics isoniazid-NAD adduct
4-[[1-hydroxy-2-(methanesulfonyl)-1,2-dihydro-2,3,1-benzodiazaborinin-7-yl]oxy]benzonitrile
-
5-((4-(1H-pyrrol-1-yl)phenoxy)methyl)-1,3,4-oxadiazole-2-thiol
57% inhibition at 0.05 mM
-
5-((4-(1H-pyrrol-1-yl)phenoxy)methyl)-4-amino-2,4-dihydro-3H-1,2,4-triazole-3-thione
-
-
5-([4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]carbonyl)-1H-indole
-
5-[2-[(E)-(hydroxyimino)methyl]phenoxy]-2,1-benzoxaborol-1(3H)-ol
-
5-[3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-2-phenoxybenzamide
25% inhibition at 0.7 mM
5-[[4-(2,4,7-trichloro-9H-fluoren-9-yl)piperazin-1-yl]carbonyl]-1H-indole
-
5-[[4-(2,7-dibromo-9H-fluoren-9-yl)piperazin-1-yl]carbonyl]-1H-indole
-
5-[[4-(2,7-diiodo-9H-fluoren-9-yl)piperazin-1-yl]carbonyl]-1H-indole
-
5-[[4-(2-methoxy-9H-fluoren-9-yl)piperazin-1-yl]carbonyl]-1H-indole
-
5-[[4-(2-nitro-9H-fluoren-9-yl)piperazin-1-yl]carbonyl]-1H-indole
-
5-[[4-(3-nitro-9H-fluoren-9-yl)piperazin-1-yl]carbonyl]-1H-indole
-
5-[[4-(4-methoxy-9H-fluoren-9-yl)piperazin-1-yl]carbonyl]-1H-indole
-
5-[[4-(9H-fluoren-9-yl)piperazin-1-yl]carbonyl]-1H-indole
-
7-[2-[(Z)-(hydroxyimino)methyl]-4-(trifluoromethyl)phenoxy]-2-(methanesulfonyl)-2,3,1-benzodiazaborinin-1(2H)-ol
-
9-[4-(1H-indol-5-ylcarbonyl)piperazin-1-yl]-N,N-dimethyl-9H-fluoren-2-amine
-
betulinic acid
inhibitor identified by in silico screening, MIC value 0.1 mg/ml
carfilzomib
proteasome inhibitor, shows a high binding affinity and binds strongly to the active sites of Klebsiella pneumoniae FabI and FabV proteins, and Mycobacterium tuberculosis InhA
Colchicine
inhibitor identified by in silico screening, MIC value 0.1 mg/ml
embelin
inhibitor identified by in silico screening, MIC value 0.1 mg/ml
ethionamide-NAD adduct
in its active form, ethionamide forms covalent adduct with NAD, which competitively inhibits the enzyme
-
icariin
inhibitor identified by in silico screening, MIC value 0.1 mg/ml
methyl 2-[[(1-cyclohexyl-5-oxopyrrolidin-3-yl)carbonyl]amino]benzoate
-
N'-((1H-indol-3-yl)methylene)2-(4-(1H-pyrrol-1-yl)phenoxy)acetohydrazide
19% inhibition at 0.05 mM
-
N-((4-bromo-1-ethyl-1H-pyrazol-5-yl)methyl)-4-((3,5-dimethyl-1Hpyrazol-1-yl)methyl)benzamide
-
N-(2,6-dichlorophenyl)-4-(2,5-dimethyl-1H-pyrrol-1-yl)benzamide
31% inhibition at 0.05 mM, 35% inhibition at 0.005 mM
-
N-(2-aminophenyl)-4-(2,5-dimethyl-1H-pyrrol-1-yl)benzamide
12% inhibition at 0.05 mM, 35% inhibition at 0.005 mM
-
N-(2-bromobenzyl)-4-[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]benzamide
-
N-(2-chloro-4-fluorobenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
-
N-(2-chloro-4-fluorobenzyl)-4-((4-methylthiazol-2-yl)methyl)-benzamide
-
N-(2-chloro-5-(2-phenylacetamido)benzyl)-4-((3,5-dimethyl-1Hpyrazol-1-yl)methyl)benzamide
-
N-(2-chloro-5-(3-phenylureido)benzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
-
N-(2-chloro-5-(trifluoromethyl)phenyl)-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide
-
N-(2-chloro-5-(trifluoromethyl)phenyl)-2-(4-oxoquinazolin-3(4H)-yl)acetamide
-
N-(2-chloro-5-aminobenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
-
N-(2-chlorobenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
-
N-(2-nitrobenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
-
N-(2-trifluorobenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)-benzamide
-
N-(3-benzylphenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
-
N-(3-bromobenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
-
N-(3-bromophenyl)-1-(4-fluorophenyl)-5-oxopyrrolidine-3-carboxamide
-
N-(3-bromophenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
-
N-(3-bromophenyl)-5-oxo-1-phenylpyrrolidine-3-carboxamide
-
N-(3-chloro-2-methylphenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
-
N-(3-chloro-4-fluorophenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
-
N-(3-chlorobenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
-
N-(3-chlorophenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
-
N-(3-chlorophenyl)-5-oxo-1-phenylpyrrolidine-3-carboxamide
-
N-(3-methanesulfonybenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)-methyl)benzamide
-
N-(3-propan-2-yloxybenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
-
N-(4-acetylphenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
-
N-(4-aminophenyl)-4-(2,5-dimethyl-1H-pyrrol-1-yl)benzamide
30% inhibition at 0.05 mM, 35% inhibition at 0.005 mM
-
N-(4-bromo-3-methylphenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
-
N-(4-bromophenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
-
N-(4-bromophenyl)-3-{(2E)-2-[(4-methylphenyl)methylidene]hydrazinyl}-1,2,4-thiadiazol-5-amine
-
-
N-(4-fluoro-2-(trifluoromethyl)benzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
-
N-(4-fluorobenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
-
N-(5-chloro-2-methoxyphenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
-
N-(5-chloro-2-methylphenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
-
N-(5-nitrothiazol-2-yl)-2-(4-oxoquinazolin-3(4H)-yl)acetamide
-
N-(6-nitro-1,3-benzothiazol-2-yl)-2-(4-oxoquinazolin-3(4H)-yl)acetamide
72.18% inhibition at 0.01 mM
-
N-(6-nitrobenzo[d]thiazol-2-yl)-2-(4-oxoquinazolin-3(4H)-yl)acetamide
-
N-(anthracen-9-ylmethyl)-1-bicyclo[2.2.1]hept-2-yl-N-methyl-5-oxopyrrolidine-3-carboxamide
-
N-(anthracen-9-ylmethyl)-1-cycloheptyl-N-methyl-5-oxopyrrolidine-3-carboxamide
-
N-(anthracen-9-ylmethyl)-1-cyclohexyl-N-methyl-5-oxopyrrolidine-3-carboxamide
-
N-(anthracen-9-ylmethyl)-1-cyclooctyl-N-methyl-5-oxopyrrolidine-3-carboxamide
-
N-(benzo[d]thiazol-2-yl)-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide
-
N-(benzo[d]thiazol-2-yl)-2-(4-oxoquinazolin-3(4H)-yl)acetamide
-
N-(benzo[d]thiazol-2-yl)-2-(6-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide
-
N-(benzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
-
N-(furan-2-yl-methyl)-2-(4-oxoquinazolin-3(4H)-yl)acetamide
-
N-(furan-2-ylmethyl)-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide
-
N-benzyl-4-(2,5-dimethyl-1H-pyrrol-1-yl)benzamide
12% inhibition at 0.05 mM, 35% inhibition at 0.005 mM
-
N-biphenyl-3-yl-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
-
N-[(2-chloro-4-fluorophenyl)methyl]-4-[(2-methyl-1,3-thiazol-4-yl)methyl]benzamide
-
N-[(2-chloro-4-fluorophenyl)methyl]-4-[(3-methyl-1H-pyrazol-1-yl)methyl]benzamide
-
N-[(2-chloro-4-fluorophenyl)methyl]-4-[(6-methylpyridin-2-yl)-oxy]benzamide
-
N-[(2-chloro-4-fluorophenyl)methyl]-4-[(6-methylpyridin-2-yl)methyl]benzamide
-
N-[(2-chloro-4-fluorophenyl)methyl]-4-[(6-methylpyridin-2-yl)sulfanyl]benzamide
-
N-[(2-chloro-4-fluorophenyl)methyl]-4-[(dimethyl-1,3-thiazol-2-yl)methyl]benzamide
-
N-[(2-chloro-4-fluorophenyl)methyl]-4-[2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl]benzamide
-
N-[(4-fluorophenyl)methyl]-4-[[2-methyl-5-(2,2,2-trifluoroethyl)furan-3-yl]methyl]benzamide
-
N-[2-methyl-5-phenyl-3-([4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methyl)-1H-pyrrol-1-yl]pyridine-4-carboxamide
i.e. LL3858
-
N-[3,5-bis(trifluoromethyl)phenyl]-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
-
N-[3-bromo-5-(trifluoromethyl)phenyl]-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
-
N-[4-(4-bromophenyl)-1,3-thiazol-2-yl]-4-(1H-pyrrol-1-yl)benzamide
25% inhibition at 0.05 mM, 35% inhibition at 0.005 mM
-
N-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]-4-(2,5-dimethyl-1Hpyrrol-1-yl)benzamide
38% inhibition at 0.05 mM, 35% inhibition at 0.005 mM
-
N-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-4-(2,5-dimethyl-1H-pyrrol-1-yl)benzamide
38% inhibition at 0.05 mM, 35% inhibition at 0.005 mM
-
N-[4-(4-nitrophenyl)-1,3-thiazol-2-yl]-4-(1H-pyrrol-1-yl)benzamide
30% inhibition at 0.05 mM, 35% inhibition at 0.005 mM
-
N-[4-(benzyloxy)phenyl]-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
-
N-[9-[4-(1H-indol-5-ylcarbonyl)piperazin-1-yl]-9H-fluoren-2-yl]benzamide
-
N-[9-[4-(1H-indol-5-ylcarbonyl)piperazin-1-yl]-9H-fluoren-2-yl]butanamide
-
N-[9-[4-(1H-indol-5-ylcarbonyl)piperazin-1-yl]-9H-fluoren-2-yl]formamide
-
pentacyano(isoniazid)ferrate(II)
the inorganic complex inhibits both wild-type and isoniazid-resistant Ile21Val mutants of InhA and this inactivation did not require activation by KatG. Molecular dynamics simulations show that the interaction of pentacyano(isoniazid)ferrate(II) with InhA leads to macromolecular instabilities reflected in the long time necessary for simulation convergence. These instabilities are mainly due to perturbation of the substrate binding loop, particularly the partial denaturation of helices alpha6 and alpha7
pyrrolidine carboxamide
IC50: 10.05 microM, chosen as a lead structure for further structure optimization
Trp-Tyr-Trp
structure-based computer modelling approach to design a tripeptide inhibitor. Docking studies indicate that the designed peptide has potency 100 times higher than the best known inhibitor. The results suggest that the designed inhibitor is a suitable lead compound for the development of novel anti-TB drugs
ursolic acid
inhibitor identified by in silico screening, MIC value 0.1 mg/ml
WYW
tripeptide inhibitor, identified using a structure-based approach
[4-(9H-fluoren-9-yl) piperazin-1-yl]-benzyl-methanone
0.015 mM, 97% inhibition
[4-(9H-fluoren-9-yl)piperazin-1-yl](1H-indol-5-yl)methanone
0.015 mM, 94% inhibition
[4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl](1H-indol-5-yl)methanone
0.015 mM, 67% inhibition
[4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl](4-methylphenyl)methanone
0.015 mM, 74% inhibition
[4-[(4-fluorophenyl)(phenyl)methyl]piperazin-1-yl](1H-indol-5-yl)methanone
0.015 mM, 81% inhibition
[4-[(4-fluorophenyl)(phenyl)methyl]piperazin-1-yl](phenyl)methanone
0.015 mM, 81% inhibition
[5-(3-carbamoyl-4-phenoxyphenyl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl dihydrogen phosphate
12% inhibition at 0.1 mM
[9-[4-(1H-indol-5-ylcarbonyl)piperazin-1-yl]-9H-fluoren-2-yl]carbamic acid
-
(2E)-3-(6-aminopyridin-3-yl)-N-methyl-N-[(1-methyl-1H-indol-2-yl)methyl]prop-2-enamide
-
-
(2E)-3-[4-(benzyloxy)phenyl]-2-cyano-N-(6-methylpyridin-2-yl)prop-2-enamide
-
-
(2E)-N-(1H-indol-3-ylmethyl)-N-methyl-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)prop-2-enamide
-
-
(2E)-N-methyl-N-[(3-methyl-1-benzofuran-2-yl)methyl]-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)prop-2-enamide
-
-
(2S,3R)-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3,4-dihydro-2H-chromen-3-yl 3,4,5-trihydroxybenzoate
-
-
(2S,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl 3,4,5-trihydroxybenzoate
-
-
(3aR,4S,6aR)-3,3a,4,6a-tetrahydro-2H-cyclopenta[b]furan-4,5-diyldimethanol
-
-
(4S)-1-(2,4-dimethylphenyl)-4-(3-{4-[(propan-2-yl)oxy]phenyl}-1,2,4-oxadiazol-5-yl)pyrrolidin-2-one
-
-
(4S)-1-(3,4-dimethylphenyl)-4-(3-{4-[(propan-2-yl)oxy]phenyl}-1,2,4-oxadiazol-5-yl)pyrrolidin-2-one
-
-
(E)-2-(2-ionicotinoylhydrazineylidene)-N-(3,4,5-trichlorophenyl)propanamide
-
-
-
(E)-2-(2-isonicotinoylhydrazineylidene)-N-[3-(trifluoromethoxy)phenyl]propanamide
-
-
-
(E)-2-(2-isonicotinoylhydrazineylidene)-N-[3-(trifluoromethyl)phenyl]propanamide
-
-
-
(E)-2-(2-isonicotinoylhydrazineylidene)-N-[4-(perfluorooctyl)phenyl]propanamide
-
-
-
(E)-2-(2-isonicotinoylhydrazineylidene)-N-[4-(trifluoromethoxy)phenyl]propanamide
-
-
-
(E)-2-(2-isonicotinoylhydrazineylidene)-N-[4-(trifluoromethyl)phenyl]propanamide
-
-
-
(E)-2-(2-isonicotinoylhydrazineylidene)-N-{4-[(trifluoromethyl)thio]phenyl}propanamide
-
-
-
(E)-N-(3,4-dichlorophenyl)-2-(2-isonicotinoylhydrazineylidene)propanamide
-
-
-
(E)-N-(3,4-difluorophenyl)-2-(2-isonicotinoylhydrazineylidene)propanamide
-
-
-
(E)-N-(3,5-dichlorophenyl)-2-(2-isonicotinoylhydrazineylidene)propanamide
-
-
-
(E)-N-(3-bromophenyl)-2-(2-isonicotinoylhydrazineylidene)propanamide
-
-
-
(E)-N-(3-chlorophenyl)-2-(2-isonicotinoylhydrazineylidene)propanamide
-
-
-
(E)-N-(3-fluorophenyl)-2-(2-isonicotinoylhydrazineylidene)propanamide
-
-
-
(E)-N-(3-iodophenyl)-2-(2-isonicotinoylhydrazineylidene)propanamide
-
-
-
(E)-N-(4-bromophenyl)-2-(2-isonicotinoylhydrazineylidene)propanamide
-
-
-
(E)-N-(4-chlorophenyl)-2-(2-isonicotinoylhydrazineylidene)propanamide
-
-
-
(E)-N-(4-fluorophenyl)-2-(2-isonicotinoylhydrazineylidene)propanamide
-
-
-
(E)-N-(4-iodophenyl)-2-(2-isonicotinoylhydrazineylidene)propanamide
-
-
-
(E)-N-[3,5-bis(trifluoromethyl)phenyl]-2-(2-isonicotinoylhydrazineylidene)propanamide
-
-
-
(E)-N-[4-(difluoromethoxy)phenyl]-2-(2-isonicotinoylhydrazineylidene)propanamide
-
-
-
(RS)-1-hydroxy-1-[3-(octadecyloxy)-phenyl]-1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-3-one
-
28% inhibition at 0.03 mM, IC50 for growth of Mycobacterium tuberculosis is 0.012 mM
(RS)-1-[3-(dodecylsulfanyl)phenyl]-1-hydroxy-1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-3-one
-
15% inhibition at 0.03 mM, IC50 for growth of Mycobacterium tuberculosis is 0.0065 mM
1-(3-amino-2-methylbenzyl)-4-(2-thiophen-2-ylethoxy)pyridin-2(1H)-one
-
-
1-(4-methyl-1,3-thiazol-2-yl)-1-(5-[[6-(morpholin-4-yl)pyridin-2-yl]amino]-1,3,4-thiadiazol-2-yl)ethan-1-ol
-
-
1-(4-methyl-1,3-thiazol-2-yl)-1-(5-[[6-(piperidin-1-yl)pyridin-2-yl]amino]-1,3,4-thiadiazol-2-yl)ethan-1-ol
-
-
1-(4-methyl-1,3-thiazol-2-yl)-1-(5-[[6-(trifluoromethyl)pyridin-2-yl]amino]-1,3,4-thiadiazol-2-yl)ethan-1-ol
-
-
1-(4-methyl-1,3-thiazol-2-yl)-1-[5-[(1-methyl-1H-1,2,3-triazol-4-yl)amino]-1,3,4-thiadiazol-2-yl]ethan-1-ol
-
-
1-(4-methyl-1,3-thiazol-2-yl)-1-[5-[(pyridin-2-yl)amino]-1,3,4-thiadiazol-2-yl]ethan-1-ol
-
-
1-(4-methyl-1,3-thiazol-2-yl)-1-[5-[(pyrimidin-2-yl)amino]-1,3,4-thiadiazol-2-yl]ethan-1-ol
-
-
1-(5-[[5-bromo-6-(trifluoromethyl)pyridin-2-yl]amino]-1,3,4-thiadiazol-2-yl)-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
-
-
1-(cyclohexylmethyl)-3-(2,6-dichlorobenzyl)-2-methylpyridin-4(1H)-one
-
-
1-cyclohexyl-N-(2'-hydroxy-1,1':3',1''-terphenyl-5'-yl)-5-oxopyrrolidine-3-carboxamide
-
-
1-[4-(2,4-dichlorophenoxy)-3-hydroxyphenyl]-2-phenylethan-1-one
-
-
1-[5-(3-bromo-4-fluoroanilino)-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
-
-
1-[5-[(1-methyl-1H-pyrazol-3-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
-
-
1-[5-[(1-methyl-1H-pyrazol-4-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
-
-
1-[5-[(2-methoxypyridin-4-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
-
-
1-[5-[(2-methylpyridin-3-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
-
-
1-[5-[(5-bromo-6-methylpyridin-2-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
-
-
1-[5-[(5-bromopyridin-2-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
-
-
1-[5-[(5-fluoropyridin-2-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
-
-
1-[5-[(5-methylpyridin-3-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
-
-
1-[5-[(6-bromopyridin-2-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
-
-
1-[5-[(6-cyclopropylpyridin-2-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
-
-
1-[5-[(6-fluoropyridin-2-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
-
-
1-[5-[(6-methoxypyridin-2-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
-
-
1-[5-[(6-methylpyridin-2-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
-
-
1-[5-[(6-methylpyridin-3-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
-
-
2-(2,4-dichlorophenoxy)-5-(hexylamino)phenol
-
73% inhibition at 1 mM
2-(2,4-dichlorophenoxy)-5-[(1H-1,2,3-triazol-1-yl)methyl]phenol
-
97% inhibition at 1 mM
2-(2,4-dichlorophenoxy)-5-[5-(trimethylsilyl)-1,2-oxazol-3-yl]phenol
-
complete inhibition at 1 mM
2-[(2-fluorophenyl)methyl]-N-[(1S)-1-(2-methyl-1,3-thiazol-4-yl)ethyl]-1,3-benzoxazole-5-carboxamide
-
-
2-[2-(dimethylamino)-4-sulfanylphenoxy]-5-{[(2-phenylethyl)amino]methyl}phenol
-
-
2-[2-[4-(1H-pyrrol-1-yl)benzoyl]hydrazineylidene]-N-(4-fluorophenyl)propanamide
-
-
-
2-[4-(2,4-dinitrophenyl)-1H-pyrazol-1-yl]-4-(trifluoromethyl)pyrimidine
-
-
2-[4-({[(2,3-dihydro-1-benzofuran-6-yl)methyl]amino}methyl)-2-hydroxyphenoxy]-5-methylbenzonitrile
-
-
2-{4-[(4-benzyl-1H-1,2,3-triazol-1-yl)methyl]-2-chlorophenoxy}-5-chlorophenol
-
-
2-{4-[(4-butyl-1H-1,2,3-triazol-1-yl)methyl]-2-chlorophenoxy}-5-chlorophenol
-
-
2-{4-[(5-benzyl-1,2-oxazol-3-yl)methyl]-2-chlorophenoxy}-5-chlorophenol
-
-
2-{4-[(5-butyl-1,2-oxazol-3-yl)methyl]-2-chlorophenoxy}-5-chlorophenol
-
-
3'-methyl-4-[2-(methylamino)-4-(3-methylbutyl)phenoxy][1,1'-biphenyl]-3-ol
-
-
3'-methyl-4-[2-(methylamino)-4-(propan-2-yl)phenoxy][1,1'-biphenyl]-3-ol
-
-
3'-methyl-4-{[3-(methylamino)[1,1'-biphenyl]-4-yl]oxy}[1,1'-biphenyl]-3-ol
-
-
3-(2-(4-methylbenzylidene)hydrazinyl)-N-(2-(trifluoromethyl)phenyl)-1,2,4-thiadiazol-5-amine
-
64% inhibition at 0.05 mM, 35% inhibition at 0.005 mM
-
3-(2-(4-methylbenzylidene)hydrazinyl)-N-(4-nitrophenyl)-1,2,4-thiadiazol-5-amine
-
8% inhibition at 0.05 mM
-
3-(2-(4-methylbenzylidene)hydrazinyl)-N-(p-tolyl)-1,2,4-thiadiazol-5-amine
-
21% inhibition at 0.05 mM
-
3-(2-(4-methylbenzylidene)hydrazinyl)-N-phenyl-1,2,4-thiadiazol-5-amine
-
34% inhibition at 0.05 mM
-
3-(2-benzylidenehydrazinyl)-N-(2,4-dichlorophenyl)-1,2,4-thiadiazol-5-amine
-
38% inhibition at 0.05 mM
-
3-(2-benzylidenehydrazinyl)-N-(2-(trifluoromethyl)phenyl)-1,2,4-thiadiazol-5-amine
-
50% inhibition at 0.05 mM
-
3-(2-benzylidenehydrazinyl)-N-(4-bromophenyl)-1,2,4-thiadiazol-5-amine
-
61% inhibition at 0.05 mM, 39% inhibition at 0.005 mM
-
3-(2-benzylidenehydrazinyl)-N-(4-fluorophenyl)-1,2,4-thiadiazol-5-amine
-
54% inhibition at 0.05 mM
-
3-(2-benzylidenehydrazinyl)-N-(4-iodophenyl)-1,2,4-thiadiazol-5-amine
-
-
-
3-(2-benzylidenehydrazinyl)-N-(4-methoxyphenyl)-1,2,4-thiadiazol-5-amine
-
46% inhibition at 0.05 mM
-
3-(2-benzylidenehydrazinyl)-N-(4-nitrophenyl)-1,2,4-thiadiazol-5-amine
-
35% inhibition at 0.05 mM
-
3-(2-benzylidenehydrazinyl)-N-(p-tolyl)-1,2,4-thiadiazol-5-amine
-
75% inhibition at 0.05 mM, 48% inhibition at 0.005 mM
-
3-(2-benzylidenehydrazinyl)-N-phenyl-1,2,4-thiadiazol-5-amine
-
16% inhibition at 0.05 mM
-
3-(4-methoxyphenyl)-N-(6-phenylimidazo[2,1-b][1,3,4]thiadiazol-2-yl)propanamide
-
-
3-chloro-4-[2-hydroxy-4-[(2-methylphenyl)methyl]phenoxy]benzonitrile
-
-
3-chloro-4-[2-hydroxy-4-[(pyridin-4-yl)methyl]phenoxy]benzonitrile
-
-
4-(2,4-dichlorophenoxy)-3-hydroxybenzonitrile
-
97% inhibition at 1 mM
4-[(3'-methoxy[1,1'-biphenyl]-3-yl)carbamoyl]-1-(3-methylbut-2-en-1-yl)piperidin-1-ium
-
-
4-[(3-ethyl[1,1'-biphenyl]-4-yl)oxy]-3'-methyl[1,1'-biphenyl]-3-ol
-
-
4-[2-(dimethylamino)-4-(3-methylbutyl)phenoxy]-3'-methyl[1,1'-biphenyl]-3-ol
-
-
4-[2-(dimethylamino)-4-(propan-2-yl)phenoxy]-3'-methyl[1,1'-biphenyl]-3-ol
-
-
4-[2-ethyl-4-(3-methylbutyl)phenoxy]-3'-methyl[1,1'-biphenyl]-3-ol
-
-
4-[2-ethyl-4-(propan-2-yl)phenoxy]-3'-methyl[1,1'-biphenyl]-3-ol
-
-
4-[2-[(3-cyano-4,6-dithiophen-2-ylpyridin-2-yl)sulfanyl]ethyl]benzoic acid
-
-
4-[4-({[2-(4-chlorophenyl)ethyl]amino}methyl)-2-hydroxyphenoxy]-3-(methylamino)anilinium
-
-
4-{4-[(benzylamino)methyl]-2-hydroxyphenoxy}-3-chlorobenzonitrile
-
-
4-{[3-(dimethylamino)[1,1'-biphenyl]-4-yl]oxy}-3'-methyl[1,1'-biphenyl]-3-ol
-
-
5-(anilinomethyl)-2-[2-(dimethylamino)-4-(3-methylbutyl)phenoxy]phenol
-
-
5-(anilinomethyl)-2-[2-(dimethylamino)-4-(propan-2-yl)phenoxy]phenol
-
-
5-(anilinomethyl)-2-[2-(methylamino)-4-(3-methylbutyl)phenoxy]phenol
-
-
5-(anilinomethyl)-2-[2-(methylamino)-4-(propan-2-yl)phenoxy]phenol
-
-
5-(anilinomethyl)-2-{[3-(dimethylamino)[1,1'-biphenyl]-4-yl]oxy}phenol
-
-
5-(anilinomethyl)-2-{[3-(methylamino)[1,1'-biphenyl]-4-yl]oxy}phenol
-
-
5-(benzylamino)-2-(2,4-dichlorophenoxy)phenol
-
25% inhibition at 1 mM
5-(cyclohexylamino)-2-(2,4-dichlorophenoxy)phenol
-
12.5% inhibition at 1 mM
5-(cyclohexylmethyl)-2-[(3-ethyl[1,1'-biphenyl]-4-yl)oxy]phenol
-
-
5-(cyclohexylmethyl)-2-[2-(dimethylamino)-4-(3-methylbutyl)phenoxy]phenol
-
-
5-(cyclohexylmethyl)-2-[2-(dimethylamino)-4-(propan-2-yl)phenoxy]phenol
-
-
5-(cyclohexylmethyl)-2-[2-(methylamino)-4-(3-methylbutyl)phenoxy]phenol
-
-
5-(cyclohexylmethyl)-2-[2-(methylamino)-4-(propan-2-yl)phenoxy]phenol
-
-
5-(cyclohexylmethyl)-2-[2-ethyl-4-(3-methylbutyl)phenoxy]phenol
-
-
5-(cyclohexylmethyl)-2-{[3-(dimethylamino)[1,1'-biphenyl]-4-yl]oxy}phenol
-
-
5-(cyclohexylmethyl)-2-{[3-(methylamino)[1,1'-biphenyl]-4-yl]oxy}phenol
-
-
5-({[(2,3-dihydro-1-benzofuran-6-yl)methyl]amino}methyl)-2-[2-methyl-4-(methylamino)phenoxy]phenol
-
-
5-({[2-(4-chlorophenyl)ethyl]amino}methyl)-2-[2-(dimethylamino)-4-ethylphenoxy]phenol
-
-
5-({[2-(4-chlorophenyl)ethyl]amino}methyl)-2-[2-ethyl-4-(sulfanylmethyl)phenoxy]phenol
-
-
5-benzyl-N-{[3-chloro-4-(4-chloro-2-hydroxyphenoxy)phenyl]methyl}-1,2-oxazole-3-carboxamide
-
-
5-chloro-2-{2-chloro-4-[(1H-1,2,3-triazol-1-yl)methyl]phenoxy}phenol
-
-
5-chloro-2-{2-chloro-4-[(hexylamino)methyl]phenoxy}phenol
-
38% inhibition at 1 mM
5-[(4-benzyl-1H-1,2,3-triazol-1-yl)methyl]-2-(2,4-dichlorophenoxy)phenol
-
-
5-[(4-butyl-1H-1,2,3-triazol-1-yl)methyl]-2-(2,4-dichlorophenoxy)phenol
-
98% inhibition at 1 mM
5-[(benzylamino)methyl]-2-[2-(dimethylamino)-4-ethylphenoxy]phenol
-
-
6-([5-[1-hydroxy-1-(4-methyl-1,3-thiazol-2-yl)ethyl]-1,3,4-thiadiazol-2-yl]amino)pyridin-2-ol
-
-
N'-[(Z)-[3-(4-methoxyphenyl)-1H-pyrazol-4-yl]methylidene]-2,8-dimethylquinoline-4-carbohydrazide
-
-
N-(2,4-dichlorophenyl)-3-(2-(4-methylbenzylidene)hydrazinyl)-1,2,4-thiadiazol-5-amine
-
62% inhibition at 0.05 mM, 48% inhibition at 0.005 mM
-
N-(2-phenoxyphenyl)-2-[2-(pyridin-2-yl)-1,3-thiazol-4-yl]acetamide
-
-
N-(4-bromo-3-methylphenyl)-2-[2-(thiophen-3-yl)-1,3-thiazol-4-yl]acetamide
-
-
N-(4-bromophenyl)-3-(2-(4-methylbenzylidene)hydrazinyl)-1,2,4-thiadiazol-5-amine
-
46% inhibition at 0.05 mM
-
N-(4-fluorophenyl)-3-(2-(4-methylbenzylidene)hydrazinyl)-1,2,4-thiadiazol-5-amine
-
67% inhibition at 0.05 mM, 26% inhibition at 0.005 mM
-
N-(4-iodophenyl)-3-(2-(4-methylbenzylidene)hydrazinyl)-1,2,4-thiadiazol-5-amine
-
34% inhibition at 0.05 mM
-
N-(4-methoxyphenyl)-3-(2-(4-methylbenzylidene)hydrazinyl)-1,2,4-thiadiazol-5-amine
-
50% inhibition at 0.05 mM
-
N-(4-[5-[(2-methylphenoxy)methyl]-1,2,4-oxadiazol-3-yl]phenyl)thiophene-2-carboxamide
-
-
N-[2-(4-anilinoanilino)-2-oxoethyl]-2H-1,3-benzodioxole-5-carboxamide
-
-
N-{[3-chloro-4-(4-chloro-2-hydroxyphenoxy)phenyl]methyl}-2-(3-methyl-1,2-oxazol-5-yl)acetamide
-
-
N-{[3-chloro-4-(4-chloro-2-hydroxyphenoxy)phenyl]methyl}-5-methyl-1,2-oxazole-3-carboxamide
-
-
N-{[4-(2,4-dichlorophenoxy)-3-hydroxyphenyl]methyl}-5-methyl-1,2-oxazole-3-carboxamide
-
more than 80% inhibition at 1 mM
Na3[Fe(CN)5(isonicotinic acid hydrazide)]4H2O
-
time dependent inactivation, rate constant value 327/min
panosialin A
-
acylbenzenediol sulfate metabolites from Streptomyces sp. AN1761, potently inhibits bacterial enoyl-ACP reductases of Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis
panosialin B
-
acylbenzenediol sulfate metabolites from Streptomyces sp. AN1761, potently inhibits bacterial enoyl-ACP reductases of Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis
panosialin wA
-
acylbenzenediol sulfate metabolites from Streptomyces sp. AN1761, potently inhibits bacterial enoyl-ACP reductases of Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis
panosialin wB
-
acylbenzenediol sulfate metabolites from Streptomyces sp. AN1761, potently inhibits bacterial enoyl-ACP reductases of Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis
pentacyano(isoniazid)ferrate(II)
-
inhibits both wild-type and isoniazid-resistant I21V mutants of InhA. Inactivation does not require activation by KatG. Compound strongly interacts with InhA, the interactions lead to macromolecular instabilities reflected in the long time necessary for simulation convergence. The instabilities are mainly due to perturbation of the substrate binding loop, particularly the partial denaturation of helices alpha6 and alpha7. The association of the inhibitor with enzyme is very strong in the first 20.0 ns, but becomes very week at the end of the moleculár dynamics simulation
pentacyano(isoniazid)ferrateII complex
-
Na3[FeII(CN)5(INH)]*3H2O complex
-
[4-(2,4-dichlorophenoxy)-3-hydroxyphenyl](morpholin-4-yl)methanone
-
-
2-(6-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)-N-phenylacetamide
-
2-(6-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)-N-phenylacetamide
88.12% inhibition at 0.01 mM
2-(6-chloro-4-oxoquinazolin-3(4H)-yl)-N-phenylacetamide
58.34% inhibition at 0.01 mM
2-(o-tolyloxy)-5-hexylphenol
i.e. PT70, a slow, tight binding inhibitor of InhA. PT70 binds preferentially to the InhA-NAD+ complex, binding structure, overview. It has a residence time of 24 min on the target, which is 14000times longer than that of the rapid reversible inhibitor from which it is derived. The slow onset inhibition is coupled to ordering of an active site loop, which leads to the closure of the substrate-binding pocke
2-(o-tolyloxy)-5-hexylphenol
i.e. PT70, slow, tight binding inhibitor. It binds preferentially to the enzyme/NAD+x01complex and has a residence time of 24 min on the target, which is 14000 times longer than that of the rapid reversible inhibitor from which it is derived. The 1.8 A crystal structure of the ternary complex between InhA, NAD+, and PT70 reveals the molecular details of enzyme inhibitor recognition and supports the hypothesis that slow onset inhibition is coupled to ordering of an active site loop, which leads to the closure of the substrate-binding pocket
isoniazid
inhibition involves a covalent attachment of the activated form of the drug to the nicotinamide ring of NADH
isoniazid
inhibits InhA via formation of a covalent adduct with NAD+. KatG, the mycobacterial catalase-peroxidase, is essential for isoniazid activation. While cross-linking studies indicate that enzyme inhibition causes dissociation of the InhA tetramer into dimers, analytical ultracentrifugation and size exclusion chromatography reveal that ligand binding causes a conformational change in the protein that prevents cross-linking across one of the dimer-dimer interfaces in the InhA tetramer
isoniazid
prodrug which is biologically activated by the Mycobacterium tuberculosis catalase-peroxidase KatG enzyme. The activation reaction promotes the formation of an isonicotinyl-NAD adduct which inhibits the InhA enzyme, resulting in reduction of mycolic acid biosynthesis
triclosan
binding of triclosan to wild-type InhA is uncompetitive with respect to both NADH and trans-2-dodecenoyl-CoA. Replacement of Y158, the catalytic tyrosine residue, with Phe, reduces the affinity of triclosan for the enzyme and results in noncompetitive inhibition. I47T and I21V, two InhA mutations that occur in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis, show unimpaired inhibition by triclosan, with uncompetitive inhibition constants
triclosan
complete inhibition at 0.05 mM, 58% inhibition at 0.0005 mM
isoniazid
-
fast and efficient inhibition of InhA in the presence of NADH and INH using MnIII-pyrophosphate as nonenzymatic reagent. This chemical oxidant might be a useful tool for further mechanistic studies of isoniazid activation in attempts to establish the exact structures of isoniazid reactive species and InhA inhibitor complex(es).
triclosan
-
demonstration of triclosan inhibition of InhA in yeast represents a meaningful variation in studying this effect in mycobacteria, because it occurrs without the potentially confusing aspects of perturbing protein-protein interactions which are presumed vital to mycobacterial FASII, inactivating other important enzymes or eliciting a dedicated transcriptional response in Mycobacterium tuberculosis
additional information
28 2-(4-oxoquinazolin-3(4H)-yl)acetamide derivatives are synthesized and evaluated for their in vitro Mycobacterium tuberculosis InhA inhibition. Compounds are evaluated for their in vitro activity against drug sensitive and resistant Mycobacterium tuberculosis strains and cytotoxicity against RAW 264.7 cell line. Compounds are docked at the active site of InhA to understand their binding mode and differential scanning fluorimetry is performed to ascertain their protein interaction and stability
-
additional information
-
28 2-(4-oxoquinazolin-3(4H)-yl)acetamide derivatives are synthesized and evaluated for their in vitro Mycobacterium tuberculosis InhA inhibition. Compounds are evaluated for their in vitro activity against drug sensitive and resistant Mycobacterium tuberculosis strains and cytotoxicity against RAW 264.7 cell line. Compounds are docked at the active site of InhA to understand their binding mode and differential scanning fluorimetry is performed to ascertain their protein interaction and stability
-
additional information
a series of piperazine derivatives is synthesized and screened as MtInhA inhibitors, which results in the identification of compounds with IC50 values in the submicromolar range
-
additional information
-
a series of piperazine derivatives is synthesized and screened as MtInhA inhibitors, which results in the identification of compounds with IC50 values in the submicromolar range
-
additional information
not inhibited by N-(4-phenyl-1,3-thiazol-2-yl)-4-(1H-pyrrol-1-yl)benzamide
-
additional information
-
not inhibited by 4-hydroxyanthecotulide and 4-acetoxyanthecotulide
-
additional information
-
the heterologous enzyme is ectopically expressed in a yeast mutant strain from which the native gene encoding the corresponding mitochondrial FASII enzyme is missing.Using an appropriate fungal mitochondrial leader sequence, the mycobacterial protein is directed to the mitochondria, where it can rescue the respiratory growth phenotype of the mutant. The rationale behind the assay is that added antimycolates are foreseen to inhibit the mycobacterial enzyme, thereby recreating the respiratory deficiency of the original mutant, discernible as poor colony formation and growth on glycerol medium
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0196
trans-2-dodecenoyl-CoA
pH 7.5, 25°C, mutant enzyme T266D
0.0203
trans-2-dodecenoyl-CoA
pH 7.5, 25°C, mutant enzyme T266E
0.036
trans-2-dodecenoyl-CoA
pH 6.8, 25°C, mutant enzyme I47T
0.0409
trans-2-dodecenoyl-CoA
pH 7.5, 25°C, wild-type enzyme
0.046
trans-2-dodecenoyl-CoA
pH 6.8, 25°C, wild-type enzyme
0.0523
trans-2-dodecenoyl-CoA
pH 7.5, 25°C, mutant enzyme T266A
0.07
trans-2-dodecenoyl-CoA
pH 6.8, 25°C, mutant enzyme I21V
0.07
trans-2-dodecenoyl-CoA
pH 6.8, 25°C, mutant enzyme Y158F
0.104
trans-2-dodecenoyl-CoA
pH 6.8, 25°C, mutant enzyme S94A
additional information
additional information
-
Km values in various mutants
-
additional information
additional information
-
Km values for NADH in various mutants
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
Kcat values in various mutants
-
0.35
trans-2-dodecenoyl-CoA
pH 6.8, 25°C, mutant enzyme Y158F
1.46
trans-2-dodecenoyl-CoA
pH 7.5, 25°C, mutant enzyme T266D
2.49
trans-2-dodecenoyl-CoA
pH 7.5, 25°C, mutant enzyme T266E
7.12
trans-2-dodecenoyl-CoA
pH 7.5, 25°C, mutant enzyme T266A
15.4
trans-2-dodecenoyl-CoA
pH 6.8, 25°C, mutant enzyme I21V
16.55
trans-2-dodecenoyl-CoA
pH 6.8, 25°C, mutant enzyme S94A
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
74.49
trans-2-dodecenoyl-CoA
pH 7.5, 25°C, mutant enzyme T266D
122.7
trans-2-dodecenoyl-CoA
pH 7.5, 25°C, mutant enzyme T266E
130.6
trans-2-dodecenoyl-CoA
pH 7.5, 25°C, wild-type enzyme
136.13
trans-2-dodecenoyl-CoA
pH 7.5, 25°C, mutant enzyme T266A
148.3
trans-2-dodecenoyl-CoA
pH 6.8, 25°C, mutant enzyme S94A
181.52
trans-2-dodecenoyl-CoA
pH 6.8, 25°C, wild-type enzyme
220
trans-2-dodecenoyl-CoA
pH 6.8, 25°C, mutant enzyme I21V
333.3
trans-2-dodecenoyl-CoA
pH 6.8, 25°C, mutant enzyme I47T
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
inhibition kinetics, overview
-
0.000000022
2-(o-tolyloxy)-5-hexylphenol
pH 6.8, temperature not specified in the publication
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.099
(2E)-1-[4-(1H-pyrrol-1-yl)phenyl]-3-[4-(trifluoromethyl)phenyl]prop-2-en-1-one
Mycobacterium tuberculosis
pH and temperature not specified in the publication
-
0.2475
(2E)-3-(4-methoxyphenyl)-1-[4-(1H-pyrrol-1-yl)phenyl]prop-2-en-1-one
Mycobacterium tuberculosis
pH and temperature not specified in the publication
-
0.198
(2E)-3-(4-methylphenyl)-1-[4-(1H-pyrrol-1-yl)phenyl]prop-2-en-1-one, (2E)-3-(6-fluorocyclohexa-1,5-dien-1-yl)-1-[4-(1H-pyrrol-1-yl)phenyl]prop-2-en-1-one
Mycobacterium tuberculosis
pH and temperature not specified in the publication
-
0.0792
(2E)-3-[(4Z)-4-ethylidenecyclohexa-1,5-dien-1-yl]-1-[4-(1H-pyrrol-1-yl)phenyl]prop-2-en-1-one
Mycobacterium tuberculosis
pH and temperature not specified in the publication
-
0.0004
(4-(9H-fluoren-9-yl) piperazin-1-yl)-(4-methylbenzyl)-methanone
Mycobacterium tuberculosis
23°C, pH not specified in the publication
0.00157
(4-(9H-fluoren-9-yl)piperazin-1-yl) (2,5-difluorophenyl)methanone
Mycobacterium tuberculosis
pH 7.0, 25°C
0.000361
(4-(9H-fluoren-9-yl)piperazin-1-yl) (2-fluorophenyl)methanone
Mycobacterium tuberculosis
pH 7.0, 25°C
0.00024
(4-(9H-fluoren-9-yl)piperazin-1-yl) (3-fluorophenyl)methanone
Mycobacterium tuberculosis
pH 7.0, 25°C
0.00025
(4-(9H-Fluoren-9-yl)piperazin-1-yl) (3-tolyl)methanone
Mycobacterium tuberculosis
pH 7.0, 25°C
0.00169
(4-(9H-fluoren-9-yl)piperazin-1-yl) (4-chlorophenyl)methanone
Mycobacterium tuberculosis
pH 7.0, 25°C
0.000397
(4-(9H-fluoren-9-yl)piperazin-1-yl) (4-fluorophenyl)methanone
Mycobacterium tuberculosis
pH 7.0, 25°C
0.0029
(4-(9H-fluoren-9-yl)piperazin-1-yl) (4-methoxyphenyl)methanone
Mycobacterium tuberculosis
pH 7.0, 25°C
0.000222
(4-(9H-fluoren-9-yl)piperazin-1-yl) (4-tolyl)methanone
Mycobacterium tuberculosis
pH 7.0, 25°C
0.000183
(4-(9H-fluoren-9-yl)piperazin-1-yl) (phenyl)methanone
Mycobacterium tuberculosis
pH 7.0, 25°C
0.00104
(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)-(1H-indole-5-carbonyl)-methanone
Mycobacterium tuberculosis
23°C, pH not specified in the publication
0.00189
(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)-(4-methylbenzyl)-methanone
Mycobacterium tuberculosis
23°C, pH not specified in the publication
0.00204
(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)-benzyl-methanone
Mycobacterium tuberculosis
23°C, pH not specified in the publication
0.05
1-(2-(4-(1H-pyrrol-1-yl)phenoxy)acetyl)-4-methylenetetrahydropyridazine-3,6-dione
Mycobacterium tuberculosis
at pH 6.8 and 25°C
-
0.0156
1-(2-bromobenzyl)-3-phenylthiourea
Mycobacterium tuberculosis
pH and temperature not specified in the publication
-
0.0177
1-(2-chlorobenzyl)-3-(4-nitrophenyl)thiourea
Mycobacterium tuberculosis
pH and temperature not specified in the publication
-
0.01387
1-(3-chlorocyclohexyl)-4-[(2-fluorophenyl)carbonyl]piperazine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00605
1-(3-chlorocyclohexyl)-4-[(3,4-dichlorophenyl)carbonyl]piperazine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00099
1-(3-chlorocyclohexyl)-4-[(3,4-dimethylphenyl)carbonyl]piperazine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00673
1-(3-chlorocyclohexyl)-4-[(3-chlorophenyl)carbonyl]piperazine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00943
1-(3-chlorocyclohexyl)-4-[(3-methylphenyl)carbonyl]piperazine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00974
1-(3-chlorocyclohexyl)-4-[(4-fluorophenyl)carbonyl]piperazine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00307
1-(3-chlorocyclohexyl)-4-[(4-methylphenyl)carbonyl]piperazine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00009
1-(9H-fluoren-9-yl)-4-(phenylcarbonyl)piperazine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.0004
1-(9H-fluoren-9-yl)-4-[(4-methylphenyl)carbonyl]piperazine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.0315
1-(cyclohexylmethyl)-4-(phenylcarbonyl)piperazine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.000845
1-bicyclo[2.2.1]hept-2-yl-N-biphenyl-3-yl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00036
1-cycloheptyl-N-(2'-hydroxy-1,1':3',1''-terphenyl-4'-yl)-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.0051
1-cyclohexyl-4-(2,3-dihydro-1H-indol-1-ylcarbonyl)pyrrolidin-2-one
Mycobacterium tuberculosis
-
0.03886
1-cyclohexyl-4-(phenylcarbonyl)piperazine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00641
1-cyclohexyl-4-([4-[(4-fluorophenyl)(phenyl)methyl]piperazin-1-yl]carbonyl)pyrrolidin-2-one
Mycobacterium tuberculosis
-
0.00518
1-cyclohexyl-4-([4-[(4-methylphenyl)(phenyl)methyl]piperazin-1-yl]carbonyl)pyrrolidin-2-one
Mycobacterium tuberculosis
-
0.01762
1-cyclohexyl-4-[(3,4-dichlorophenyl)carbonyl]piperazine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.01664
1-cyclohexyl-4-[(4-methylphenyl)carbonyl]piperazine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.01066
1-cyclohexyl-5-oxo-N-phenylpyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00351
1-cyclohexyl-5-oxo-N-[3-(trifluoromethyl)phenyl]pyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.05602
1-cyclohexyl-N-(2,4-dichlorophenyl)-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.0565
1-cyclohexyl-N-(2,5-dichlorophenyl)-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.01005
1-cyclohexyl-N-(2,5-dimethylphenyl)-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.03137
1-cyclohexyl-N-(2-methyl-4-nitrophenyl)-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00039
1-cyclohexyl-N-(3,5-dichlorophenyl)-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00149
1-cyclohexyl-N-(3,5-difluorophenyl)-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00314
1-cyclohexyl-N-(3,5-dimethylphenyl)-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.000062
1-cyclohexyl-N-(3,5-diphenyl-4-hydroxyl)phenyl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
best inhibitor of the sreening with an IC50: 62 nanoM
0.01679
1-cyclohexyl-N-(3-methylphenyl)-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.01059
1-cyclohexyl-N-(3-nitrophenyl)-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.0145
1-cyclohexyl-N-(4-iodophenyl)-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00257
1-cyclohexyl-N-(9-ethyl-9H-carbazol-2-yl)-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00139
1-cyclohexyl-N-9H-fluoren-4-yl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00014
1-cyclohexyl-N-[(2'-hydroxy-1,1':3',1''-terphenyl-5'-yl)methyl]-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00555
1-cyclohexyl-N-[3-(1-methylethyl)phenyl]-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.0013
1-cyclohexyl-N-[3-methoxy-5-(trifluoromethyl)phenyl]-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00129
1-cyclooctyl-N-(2'-hydroxy-1,1':3',1''-terphenyl-4'-yl)-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00185
1-[(3,4-dimethylphenyl)carbonyl]-4-[3-(trifluoromethyl)cyclohexyl]piperazine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00774
1-[(3-chlorophenyl)carbonyl]-4-(cyclohexylmethyl)piperidine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.01547
1-[(3-methylphenyl)carbonyl]-4-(4-nitrocyclohexyl)piperazine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00626
1-[(4-methylphenyl)carbonyl]-4-[3-(trifluoromethyl)cyclohexyl]piperazine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00034
1-[9-[4-(1H-indol-5-ylcarbonyl)piperazin-1-yl]-9H-fluoren-1-yl]ethanone
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00204
1-[bis(4-fluorophenyl)methyl]-4-(phenylcarbonyl)piperazine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00189
1-[bis(4-fluorophenyl)methyl]-4-[(4-methylphenyl)carbonyl]piperazine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.0047
2,13-dioxapentacyclo[18.2.2.23,6.29,12.214,17]triaconta-1(22),3,5,9,11,14,16,20,23,25,27,29-dodecaene-4,15-diol
Mycobacterium tuberculosis
at pH 6.8 and 25°C
-
0.00004
2-(2-chloro-4-fluorophenyl)-N-(4-((3,5-dimethyl-1H-pyrazol-1-yl)-methyl)phenyl)acetamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00616
2-(2-methyl-4-oxoquinazolin-3(4H)-yl)-N-(6-nitrobenzo[d]thiazol-2-yl)acetamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00601
2-(2-methyl-4-oxoquinazolin-3(4H)-yl)-N-(thiophen-2-ylmethyl)acetamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00892
2-(2-methyl-4-oxoquinazolin-3(4H)-yl)-N-phenylacetamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.0126
2-(4-(2,5-dimethyl-1H-pyrrol-1-yl)benzoyl)-5,6,7,8-tetrabromo-2,3-dihydrophthalazine-1,4-dione
Mycobacterium tuberculosis
at pH 6.8 and 25°C
-
0.0311
2-(4-(2,5-dimethyl-1H-pyrrol-1-yl)benzoyl)-5,6,7,8-tetrachloro-2,3-dihydrophthalazine-1,4-dione
Mycobacterium tuberculosis
at pH 6.8 and 25°C
-
0.001
2-(4-chlorophenoxy)-5-(1H-1,2,3-triazol-1-yl)phenol
Mycobacterium tuberculosis
pH and temperature not specified in the publication
-
0.004
2-(4-chlorophenoxy)-5-cyclohexylphenol, 2-(4-chlorophenoxy)-5-hexylphenol
Mycobacterium tuberculosis
pH and temperature not specified in the publication
-
0.001
2-(4-chlorophenoxy)-5-[4-(1H-1,2,3-triazol-1-yl)butyl]phenol
Mycobacterium tuberculosis
pH and temperature not specified in the publication
-
0.00716
2-(6-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)-N-(2-chloro-5-(trifluoromethyl)phenyl)acetamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00452
2-(6-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)-N-(furan-2-ylmethyl)acetamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00676
2-(6-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)-N-(thiophen-2-ylmethyl)acetamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00452
2-(6-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)-N-[(furan-2-yl)methyl]acetamide
Mycobacterium tuberculosis
pH and temperature not specified in the publication
-
0.00456
2-(6-chloro-4-oxoquinazolin-3(4H)-yl)-N-(2-chloro-5-(trifluoromethyl)phenyl)acetamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00312
2-(6-chloro-4-oxoquinazolin-3(4H)-yl)-N-(furan-2-ylmethyl)acetamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00712
2-(6-chloro-4-oxoquinazolin-3(4H)-yl)-N-(thiophen-2-ylmethyl)acetamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00456
2-(6-chloro-4-oxoquinazolin-3(4H)-yl)-N-[2-chloro-5-(trifluoromethyl)phenyl]acetamide
Mycobacterium tuberculosis
pH and temperature not specified in the publication
-
0.0023
2-(ethanesulfonyl)-6-[2-[(E)-(hydroxyimino)methyl]-4-(trifluoromethyl)phenoxy]-2,3,1-benzodiazaborinin-1(2H)-ol
Mycobacterium tuberculosis
pH 6.8, 23°C
0.00003
2-(ethanesulfonyl)-7-[2-[(Z)-(hydroxyimino)methyl]-4-(trifluoromethyl)phenoxy]-2,3,1-benzodiazaborinin-1(2H)-ol
Mycobacterium tuberculosis
pH 6.8, 23°C
0.004
4-(4-chlorophenoxy)-3-hydroxybenzonitrile
Mycobacterium tuberculosis
pH and temperature not specified in the publication
-
0.008
4-(4-chlorophenoxy)[1,1'-biphenyl]-3-ol
Mycobacterium tuberculosis
pH and temperature not specified in the publication
-
0.01411
4-(cyclohexylmethyl)-1-[(2-fluorophenyl)carbonyl]piperidine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00739
4-(cyclohexylmethyl)-1-[(3-methylphenyl)carbonyl]piperidine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00516
4-(cyclohexylmethyl)-1-[(4-methylphenyl)carbonyl]piperidine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00447
4-([4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl]carbonyl)-1-cyclohexylpyrrolidin-2-one
Mycobacterium tuberculosis
-
0.00551
4-([4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]carbonyl)-1-cyclohexylpyrrolidin-2-one
Mycobacterium tuberculosis
-
0.079
4-[[1-hydroxy-2-(methanesulfonyl)-1,2-dihydro-2,3,1-benzodiazaborinin-7-yl]oxy]benzonitrile
Mycobacterium tuberculosis
pH 6.8, 23°C
0.00104
5-([4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]carbonyl)-1H-indole
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.012
5-[2-[(E)-(hydroxyimino)methyl]phenoxy]-2,1-benzoxaborol-1(3H)-ol
Mycobacterium tuberculosis
pH 6.8, 23°C
0.00017
5-[[4-(2,4,7-trichloro-9H-fluoren-9-yl)piperazin-1-yl]carbonyl]-1H-indole
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00012
5-[[4-(2,7-dibromo-9H-fluoren-9-yl)piperazin-1-yl]carbonyl]-1H-indole
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00013
5-[[4-(2,7-diiodo-9H-fluoren-9-yl)piperazin-1-yl]carbonyl]-1H-indole
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00052
5-[[4-(2-methoxy-9H-fluoren-9-yl)piperazin-1-yl]carbonyl]-1H-indole
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00013
5-[[4-(2-nitro-9H-fluoren-9-yl)piperazin-1-yl]carbonyl]-1H-indole
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00013
5-[[4-(3-nitro-9H-fluoren-9-yl)piperazin-1-yl]carbonyl]-1H-indole
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00052
5-[[4-(4-methoxy-9H-fluoren-9-yl)piperazin-1-yl]carbonyl]-1H-indole
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00016
5-[[4-(9H-fluoren-9-yl)piperazin-1-yl]carbonyl]-1H-indole
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.044
6-[4-(trifluoromethyl)phenoxy]-2,1-benzoxaborol-1(3H)-ol
Mycobacterium tuberculosis
pH 6.8, 23°C
0.0004
7-[2-[(Z)-(hydroxyimino)methyl]-4-(trifluoromethyl)phenoxy]-2-(methanesulfonyl)-2,3,1-benzodiazaborinin-1(2H)-ol
Mycobacterium tuberculosis
pH 6.8, 23°C
0.00091
9-[4-(1H-indol-5-ylcarbonyl)piperazin-1-yl]-N,N-dimethyl-9H-fluoren-2-amine
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.03488
methyl 2-[[(1-cyclohexyl-5-oxopyrrolidin-3-yl)carbonyl]amino]benzoate
Mycobacterium tuberculosis
-
0.00009
N-((4-bromo-1-ethyl-1H-pyrazol-5-yl)methyl)-4-((3,5-dimethyl-1Hpyrazol-1-yl)methyl)benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00054
N-(2-bromobenzyl)-4-[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.0005
N-(2-chloro-4-fluorobenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00006
N-(2-chloro-4-fluorobenzyl)-4-((4-methylthiazol-2-yl)methyl)-benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00008
N-(2-chloro-5-(2-phenylacetamido)benzyl)-4-((3,5-dimethyl-1Hpyrazol-1-yl)methyl)benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00009
N-(2-chloro-5-(3-phenylureido)benzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00906
N-(2-chloro-5-(trifluoromethyl)phenyl)-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00816
N-(2-chloro-5-(trifluoromethyl)phenyl)-2-(4-oxoquinazolin-3(4H)-yl)acetamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00035
N-(2-chloro-5-aminobenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00126
N-(2-chlorobenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00251
N-(2-nitrobenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.001
N-(2-trifluorobenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)-benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00041
N-(3-benzylphenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00158
N-(3-bromobenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.01355
N-(3-bromophenyl)-1-(4-fluorophenyl)-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00089
N-(3-bromophenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.02923
N-(3-bromophenyl)-5-oxo-1-phenylpyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.02312
N-(3-chloro-2-methylphenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.01483
N-(3-chloro-4-fluorophenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00158
N-(3-chlorobenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00135
N-(3-chlorophenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00394
N-(3-chlorophenyl)-5-oxo-1-phenylpyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00251
N-(3-methanesulfonybenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)-methyl)benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00158
N-(3-propan-2-yloxybenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.07358
N-(4-acetylphenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.03741
N-(4-bromo-3-methylphenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.02802
N-(4-bromophenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.0031
N-(4-fluorobenzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.0016
N-(5-chloro-2-methoxyphenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00097
N-(5-chloro-2-methylphenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00512
N-(6-nitro-1,3-benzothiazol-2-yl)-2-(4-oxoquinazolin-3(4H)-yl)acetamide
Mycobacterium tuberculosis
pH and temperature not specified in the publication
-
0.00512
N-(6-nitrobenzo[d]thiazol-2-yl)-2-(4-oxoquinazolin-3(4H)-yl)acetamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00046
N-(anthracen-9-ylmethyl)-1-bicyclo[2.2.1]hept-2-yl-N-methyl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00062
N-(anthracen-9-ylmethyl)-1-cycloheptyl-N-methyl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00075
N-(anthracen-9-ylmethyl)-1-cyclohexyl-N-methyl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00032
N-(anthracen-9-ylmethyl)-1-cyclooctyl-N-methyl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00836
N-(benzo[d]thiazol-2-yl)-2-(6-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00593
N-(benzyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00686
N-(furan-2-ylmethyl)-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00039
N-biphenyl-3-yl-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00009 - 0.00325
N-[(2-chloro-4-fluorophenyl)methyl]-4-[(2-methyl-1,3-thiazol-4-yl)methyl]benzamide
0.0005
N-[(2-chloro-4-fluorophenyl)methyl]-4-[(3-methyl-1H-pyrazol-1-yl)methyl]benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.0034
N-[(2-chloro-4-fluorophenyl)methyl]-4-[(6-methylpyridin-2-yl)-oxy]benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00005
N-[(2-chloro-4-fluorophenyl)methyl]-4-[(6-methylpyridin-2-yl)methyl]benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00006
N-[(2-chloro-4-fluorophenyl)methyl]-4-[(6-methylpyridin-2-yl)sulfanyl]benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.0014
N-[(2-chloro-4-fluorophenyl)methyl]-4-[(dimethyl-1,3-thiazol-2-yl)methyl]benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00032
N-[(2-chloro-4-fluorophenyl)methyl]-4-[2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl]benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00012 - 0.00025
N-[(4-fluorophenyl)methyl]-4-[[2-methyl-5-(2,2,2-trifluoroethyl)furan-3-yl]methyl]benzamide
0.00367
N-[3,5-bis(trifluoromethyl)phenyl]-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00085
N-[3-bromo-5-(trifluoromethyl)phenyl]-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00339
N-[4-(benzyloxy)phenyl]-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
Mycobacterium tuberculosis
-
0.00059
N-[9-[4-(1H-indol-5-ylcarbonyl)piperazin-1-yl]-9H-fluoren-2-yl]benzamide
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00046
N-[9-[4-(1H-indol-5-ylcarbonyl)piperazin-1-yl]-9H-fluoren-2-yl]butanamide
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.00018
N-[9-[4-(1H-indol-5-ylcarbonyl)piperazin-1-yl]-9H-fluoren-2-yl]formamide
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.01005
pyrrolidine carboxamide
Mycobacterium tuberculosis
IC50: 10.05 microM, chosen as a lead structure for further structure optimization
0.0125
triclosan
Mycobacterium tuberculosis
IC50 below 0.0125 mM, pH and temperature not specified in the publication
0.00009
[4-(9H-fluoren-9-yl) piperazin-1-yl]-benzyl-methanone
Mycobacterium tuberculosis
23°C, pH not specified in the publication
0.0002
[4-(9H-fluoren-9-yl)piperazin-1-yl](1H-indol-5-yl)methanone
Mycobacterium tuberculosis
23°C, pH not specified in the publication
0.00028
[9-[4-(1H-indol-5-ylcarbonyl)piperazin-1-yl]-9H-fluoren-2-yl]carbamic acid
Mycobacterium tuberculosis
in vitro inhibitory activity data, used as dependent variable in CoMFA nad CoMSIA analysis leading to twenty structures of putative binders
0.001
1-(4-methyl-1,3-thiazol-2-yl)-1-(5-[[6-(morpholin-4-yl)pyridin-2-yl]amino]-1,3,4-thiadiazol-2-yl)ethan-1-ol
Mycobacterium tuberculosis
-
IC 50 above 0.001 mM, at 37°C, pH not specified in the publication
0.000299
1-(4-methyl-1,3-thiazol-2-yl)-1-(5-[[6-(piperidin-1-yl)pyridin-2-yl]amino]-1,3,4-thiadiazol-2-yl)ethan-1-ol
Mycobacterium tuberculosis
-
at 37°C, pH not specified in the publication
0.000018
1-(4-methyl-1,3-thiazol-2-yl)-1-(5-[[6-(trifluoromethyl)pyridin-2-yl]amino]-1,3,4-thiadiazol-2-yl)ethan-1-ol
Mycobacterium tuberculosis
-
at 37°C, pH not specified in the publication
0.001
1-(4-methyl-1,3-thiazol-2-yl)-1-[5-[(1-methyl-1H-1,2,3-triazol-4-yl)amino]-1,3,4-thiadiazol-2-yl]ethan-1-ol
Mycobacterium tuberculosis
-
IC 50 above 0.001 mM, at 37°C, pH not specified in the publication
0.000386
1-(4-methyl-1,3-thiazol-2-yl)-1-[5-[(pyridin-2-yl)amino]-1,3,4-thiadiazol-2-yl]ethan-1-ol
Mycobacterium tuberculosis
-
at 37°C, pH not specified in the publication
0.001
1-(4-methyl-1,3-thiazol-2-yl)-1-[5-[(pyrimidin-2-yl)amino]-1,3,4-thiadiazol-2-yl]ethan-1-ol
Mycobacterium tuberculosis
-
IC 50 above 0.001 mM, at 37°C, pH not specified in the publication
0.000046
1-(5-[[5-bromo-6-(trifluoromethyl)pyridin-2-yl]amino]-1,3,4-thiadiazol-2-yl)-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
Mycobacterium tuberculosis
-
at 37°C, pH not specified in the publication
0.001
1-[5-(3-bromo-4-fluoroanilino)-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
Mycobacterium tuberculosis
-
IC 50 above 0.001 mM, at 37°C, pH not specified in the publication
0.000894
1-[5-[(1-methyl-1H-pyrazol-3-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
Mycobacterium tuberculosis
-
at 37°C, pH not specified in the publication
0.001
1-[5-[(1-methyl-1H-pyrazol-4-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
Mycobacterium tuberculosis
-
IC 50 above 0.001 mM, at 37°C, pH not specified in the publication
0.000741
1-[5-[(2-methoxypyridin-4-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
Mycobacterium tuberculosis
-
at 37°C, pH not specified in the publication
0.001
1-[5-[(2-methylpyridin-3-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
Mycobacterium tuberculosis
-
IC 50 above 0.001 mM, at 37°C, pH not specified in the publication
0.000179
1-[5-[(5-bromo-6-methylpyridin-2-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
Mycobacterium tuberculosis
-
at 37°C, pH not specified in the publication
0.000197
1-[5-[(5-bromopyridin-2-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
Mycobacterium tuberculosis
-
at 37°C, pH not specified in the publication
0.000363
1-[5-[(5-fluoropyridin-2-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
Mycobacterium tuberculosis
-
at 37°C, pH not specified in the publication
0.001
1-[5-[(5-methylpyridin-3-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
Mycobacterium tuberculosis
-
IC 50 above 0.001 mM, at 37°C, pH not specified in the publication
0.000013
1-[5-[(6-bromopyridin-2-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
Mycobacterium tuberculosis
-
at 37°C, pH not specified in the publication
0.000077
1-[5-[(6-cyclopropylpyridin-2-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
Mycobacterium tuberculosis
-
at 37°C, pH not specified in the publication
0.000551
1-[5-[(6-fluoropyridin-2-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
Mycobacterium tuberculosis
-
at 37°C, pH not specified in the publication
0.000264
1-[5-[(6-methoxypyridin-2-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
Mycobacterium tuberculosis
-
at 37°C, pH not specified in the publication
0.00026
1-[5-[(6-methylpyridin-2-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
Mycobacterium tuberculosis
-
at 37°C, pH not specified in the publication
0.001
1-[5-[(6-methylpyridin-3-yl)amino]-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethan-1-ol
Mycobacterium tuberculosis
-
IC 50 above 0.001 mM, at 37°C, pH not specified in the publication
0.00013
2-(2,4-dichlorophenoxy)-5-(2-methylbutyl)phenol
Mycobacterium tuberculosis
-
pH and temperature not specified in the publication
0.000096
2-(2,4-dichlorophenoxy)-5-(2-methylpropyl)phenol
Mycobacterium tuberculosis
-
pH and temperature not specified in the publication
0.000051
2-(2,4-dichlorophenoxy)-5-(2-phenylethyl)phenol
Mycobacterium tuberculosis
-
pH and temperature not specified in the publication
0.000063
2-(2,4-dichlorophenoxy)-5-(3-methylbutyl)phenol
Mycobacterium tuberculosis
-
pH and temperature not specified in the publication
0.000021
2-(2,4-dichlorophenoxy)-5-(3-phenylpropyl)phenol
Mycobacterium tuberculosis
-
pH and temperature not specified in the publication
0.00005
2-(2,4-dichlorophenoxy)-5-(4-phenylbutyl)phenol
Mycobacterium tuberculosis
-
pH and temperature not specified in the publication
0.00012
2-(2,4-dichlorophenoxy)-5-ethylphenol
Mycobacterium tuberculosis
-
pH and temperature not specified in the publication
0.0008
2-(2,4-dichlorophenoxy)-5-methylphenol
Mycobacterium tuberculosis
-
pH and temperature not specified in the publication
0.000091
2-(2,4-dichlorophenoxy)-5-propylphenol
Mycobacterium tuberculosis
-
pH and temperature not specified in the publication
0.0013
2-(2,4-dichlorophenoxy)-5-[(2-methylphenyl)methyl]phenol
Mycobacterium tuberculosis
-
pH and temperature not specified in the publication
0.00087
2-(2,4-dichlorophenoxy)-5-[(3-methylphenyl)methyl]phenol
Mycobacterium tuberculosis
-
pH and temperature not specified in the publication
0.01
2-(2,4-dichlorophenoxy)-5-[(4-fluorophenyl)methyl]phenol
Mycobacterium tuberculosis
-
pH and temperature not specified in the publication
0.000029
2-(2,4-dichlorophenoxy)-5-[(pyridin-2-yl)methyl]phenol
Mycobacterium tuberculosis
-
pH and temperature not specified in the publication
0.000042
2-(2,4-dichlorophenoxy)-5-[(pyridin-3-yl)methyl]phenol
Mycobacterium tuberculosis
-
pH and temperature not specified in the publication
0.018
2-[(2-fluorophenyl)methyl]-N-[(1S)-1-(2-methyl-1,3-thiazol-4-yl)ethyl]-1,3-benzoxazole-5-carboxamide
Mycobacterium tuberculosis
-
at pH 7.0 and 25°C
0.05
3-(2-benzylidenehydrazinyl)-N-(2-(trifluoromethyl)phenyl)-1,2,4-thiadiazol-5-amine
Mycobacterium tuberculosis
-
at pH 6.8 and 25°C
-
0.0098
3-(4-methoxyphenyl)-N-(6-phenylimidazo[2,1-b][1,3,4]thiadiazol-2-yl)propanamide
Mycobacterium tuberculosis
-
at pH 7.0 and 25°C
0.01
3-chloro-4-[2-hydroxy-4-[(2-methylphenyl)methyl]phenoxy]benzonitrile
Mycobacterium tuberculosis
-
pH and temperature not specified in the publication
0.000075
3-chloro-4-[2-hydroxy-4-[(pyridin-4-yl)methyl]phenoxy]benzonitrile
Mycobacterium tuberculosis
-
pH and temperature not specified in the publication
0.083
4-(7-chloroquinolin-4-yl)-2-[(diethylamino)methyl]phenol
Mycobacterium tuberculosis
-
at pH 7.0 and 25°C
0.004
4-methylthiazole
Mycobacterium tuberculosis
-
at 37°C, pH not specified in the publication
0.00011
5-(cyclohexylmethyl)-2-(2,4-dichlorophenoxy)phenol
Mycobacterium tuberculosis
-
pH and temperature not specified in the publication
0.000055
5-butyl-2-(2,4-dichlorophenoxy)phenol
Mycobacterium tuberculosis
-
pH and temperature not specified in the publication
0.0011
5-chloro-2-(2,4-dichlorophenoxy)phenol
Mycobacterium tuberculosis
-
pH and temperature not specified in the publication
0.001
6-([5-[1-hydroxy-1-(4-methyl-1,3-thiazol-2-yl)ethyl]-1,3,4-thiadiazol-2-yl]amino)pyridin-2-ol
Mycobacterium tuberculosis
-
IC 50 above 0.001 mM, at 37°C, pH not specified in the publication
0.0174
epigallocatechin gallate
Mycobacterium tuberculosis
-
in 30 mM PIPES buffer, 150 mM NaCl, 10% glycerol (pH 8.0)
0.02 - 0.087
N'-[(Z)-[3-(4-methoxyphenyl)-1H-pyrazol-4-yl]methylidene]-2,8-dimethylquinoline-4-carbohydrazide
0.05
N-(4-methoxyphenyl)-3-(2-(4-methylbenzylidene)hydrazinyl)-1,2,4-thiadiazol-5-amine
Mycobacterium tuberculosis
-
at pH 6.8 and 25°C
-
0.024
N-(4-[5-[(2-methylphenoxy)methyl]-1,2,4-oxadiazol-3-yl]phenyl)thiophene-2-carboxamide
Mycobacterium tuberculosis
-
at pH 7.0 and 25°C
0.019
N-phenyl-N'-[5-(4-propoxyphenyl)-1,3,4-thiadiazol-2-yl]urea
Mycobacterium tuberculosis
-
at pH 7.0 and 25°C
0.0118
panosialin A
Mycobacterium tuberculosis
-
pH 8.0, temperature not specified in the publication
0.0085
panosialin B
Mycobacterium tuberculosis
-
pH 8.0, temperature not specified in the publication
0.0096
panosialin wA
Mycobacterium tuberculosis
-
pH 8.0, temperature not specified in the publication
0.0091
panosialin wB
Mycobacterium tuberculosis
-
pH 8.0, temperature not specified in the publication
0.0028
triclosan
Mycobacterium tuberculosis
-
in 30 mM PIPES buffer, 150 mM NaCl, 10% glycerol (pH 8.0)
0.00312
2-(6-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)-N-phenylacetamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00312
2-(6-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)-N-phenylacetamide
Mycobacterium tuberculosis
pH and temperature not specified in the publication
0.00778
2-(6-chloro-4-oxoquinazolin-3(4H)-yl)-N-phenylacetamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00778
2-(6-chloro-4-oxoquinazolin-3(4H)-yl)-N-phenylacetamide
Mycobacterium tuberculosis
pH and temperature not specified in the publication
0.0000053
2-(o-tolyloxy)-5-hexylphenol
Mycobacterium tuberculosis
pH 6.8, temperature not specified in the publication
0.0000053
2-(o-tolyloxy)-5-hexylphenol
Mycobacterium tuberculosis
pH 6.8, 23°C, at 10 nM enzyme concentration
0.0000503
2-(o-tolyloxy)-5-hexylphenol
Mycobacterium tuberculosis
pH 6.8, 23°C, at 100 nM enzyme concentration
0.00009
N-[(2-chloro-4-fluorophenyl)methyl]-4-[(2-methyl-1,3-thiazol-4-yl)methyl]benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00025
N-[(2-chloro-4-fluorophenyl)methyl]-4-[(2-methyl-1,3-thiazol-4-yl)methyl]benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00325
N-[(2-chloro-4-fluorophenyl)methyl]-4-[(2-methyl-1,3-thiazol-4-yl)methyl]benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00012
N-[(4-fluorophenyl)methyl]-4-[[2-methyl-5-(2,2,2-trifluoroethyl)furan-3-yl]methyl]benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.00025
N-[(4-fluorophenyl)methyl]-4-[[2-methyl-5-(2,2,2-trifluoroethyl)furan-3-yl]methyl]benzamide
Mycobacterium tuberculosis
pH 6.8, 25°C
0.02
N'-[(Z)-[3-(4-methoxyphenyl)-1H-pyrazol-4-yl]methylidene]-2,8-dimethylquinoline-4-carbohydrazide
Mycobacterium tuberculosis
-
at pH 7.0 and 25°C
0.087
N'-[(Z)-[3-(4-methoxyphenyl)-1H-pyrazol-4-yl]methylidene]-2,8-dimethylquinoline-4-carbohydrazide
Mycobacterium tuberculosis
-
at pH 7.0 and 25°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.8
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
metabolism
metabolism
the enzyme catalyzes the NADH-dependent reduction of long-chain trans-2-enoyl-ACP fatty acids, an intermediate in mycolic acid biosynthesis
metabolism
the enzyme is a member of the mycobacterial type II dissociated fatty acid biosynthesis system
metabolism
the enzyme is an essential enzyme of the mycolic acid biosynthetic pathway
metabolism
the enzyme is involved in the biosynthesis of mycolic acids
metabolism
the enzyme is involved in the type II fatty acid biosynthesis pathway of Mycobacterium tuberculosis
metabolism
the NADH cofactor and the CoA thioester substrate form a covalent adduct during the InhA catalytic cycle. Residue Tyr158 is required for the stereospecificity of protonation and Thr196 is partially involved in hydride transfer and protonation
metabolism
-
the enzyme is involved in mycolic acid biosynthesis. It is part of the dissociative type 2 fatty acid synthase (FASII) system
metabolism
-
the enzyme is involved on the biosynthetic pathway for mycolic acids
metabolism
-
the enzyme is involved in the synthesis of cell wallmycolic acid
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
115900
-
wild-type enzyme, estimated by gel-filtration chromatography
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
tetramer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
InhA is phosphorylated in vitro by multiple Ser/Thr kinases on residue Thr266.. Activity of InhA is controlled via phosphorylation. Thr266 is the unique kinase phosphoacceptor, both in vitro and in vivo. The physiological relevance of Thr266 phosphorylation is demonstrated using inhA phosphoablative (T266A) or phosphomimetic (T266D/E) mutants. Enoyl reductase activity is severely impaired in the mimetic mutants in vitro, as a consequence of a reduced binding affinity to NADH. Introduction of inhA_T266D/E fails to complement growth and mycolic acid defects of an inhA-thermosensitive Mycobacterium smegmatis strain, in a similar manner to what is observed following isoniazid treatment. Phosphorylation of InhA may represent an unusual mechanism that allows Mycobacterium tuberculosis to regulate its mycolic acid content, thus offering a new approach to future anti-tuberculosis drug development
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
apoenzyme by the sitting drop vapor diffusion method using 100 mM sodium acetate, 100 mM MES pH 6.5 and 30% (w/v) polyethyleneglycol 400 or enzyme in complex with isoniazid, NAD+ or NADH by the hanging drop vapor diffusion method using 100 mM HEPES pH 7.5, 8-10% (w/v) 2-methyl-2,4-pentanediol, 50 mM sodium citrate pH 6.5
hanging drop vapor diffusion technique, formation of the ternary enzyme/NAD+x012-(o-tolyloxy)-5-hexylphenol complex
in complex with NAD and isoniazid, hanging drop vapour diffusion method,in 50 mM HEPES, pH 7.2, sodium citrate buffer and 5-10% 2-methyl-2,4-pentanediol
purified recombinant His-tagged InhA in a ternary complex with NAD+ and PT70, 10 mg/ml protein is combined with NAD and PT70 in a molar ratio of 1:5:200, mixing of euqual volumes of protein and reservoir solution, the latter containing 12-16% w/v PEG 4000, 1% DMSO, 100 mM N-(2-acetamido)iminodiacetic acid, pH 6.8, and 100-250 mM ammonium acetate, 22°C, 4 days, X-ray diffraction structure determination and analysis at 1.8-2.1 A resolution, modelling, overview
the crystal structure of the enzyme in complex with the inhibitor N-(4-methylbenzoyl)-4-benzylpiperidine reveals the binding mode of the inhibitor within the active site
wild-type enzyme, S94A, I47T and I21V mutants in complex with NADH at resolutions of 2.3 A, 2.2 A, 2.0 A, 1.9 A, respectively
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
I16T
I21V
I47T
S94A
T266A
phosphoablative mutant with activity similar to wild-type enzyme
T266D
phosphomimetic mutant with strongly reduced activity (31.4% compared to wild-type enzyme), introduction of inhA_T266D fails to complement growth and mycolic acid defects of an inhA-thermosensitive Mycobacterium smegmatis strain, in a similar manner to what is observed following isoniazid treatment
T266E
phosphomimetic mutant strongly reduced activity (29.5% compared to wild-type enzyme), introduction of inhA_T266E fails to complement growth and mycolic acid defects of an inhA-thermosensitive Mycobacterium smegmatis strain, in a similar manner to what is observed following isoniazid treatment
V78A
the isoniazid-resistant mutation increases the structural stability of the protein with higher NADH binding affinity
Y158A
decreased Kcat, unaffected Km for trans-2-dodecenoyl-CoA, lower Km for NADH
Y158F
Y158S
I16T
I21V
I47T
M155A
-
vmax for NADH is similar to that of wild-type, the M155A Vmax for trans-2-dodecenoyl-CoA is around 64% of the wild-type rate
P193A
-
mutation inactivates the ability of InhA to turn over either NADH or trans-2-dodecenoyl-CoA
S94A
W222A
-
reduction in overall enoyl reductase activity, mutant shows an increased affinity for NADH
I16T
mutation in the glycine-rich loop. Although very flexible, in the wild-type enzyme/NADH complex, the NADH molecule keeps its extended conformation firmly bound to the binding site of the enzyme. In the mutant complex, the NADH pyrophosphate moiety undergoes considerable conformational changes, reducing its interactions with its binding site and probably indicating the initial phase of ligand expulsion from the cavity
I21V
isoniazid-resistant mutant, loss of van der Waals interaction between NADH and the CD1 atom present in the valine residue leads to decrease of stability in binding of NADH in the active site of the protein
I21V
InhA mutation that occur in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis, show unimpaired inhibition by triclosan, with uncompetitive inhibition constant
I21V
mutation in the glycine-rich loop. Although very flexible, in the wild-type enzyme/NADH complex, the NADH molecule keeps its extended conformation firmly bound to the binding site of the enzyme. In the mutant complex, the NADH pyrophosphate moiety undergoes considerable conformational changes, reducing its interactions with its binding site and probably indicating the initial phase of ligand expulsion from the cavity
I21V
similar to wild-type InhA, cross-linking of the isoniazid resistant mutant gives three bands on SDS-PAGE assigned to monomer, dimer, and tetrameric forms of the protein. The inhibition of the enzyme with the isoniazid-NAD adduct results in loss of the band assigned to tetramer. In contrast, cross-linking in the presence of saturating concentrations of NADH yields a lower amount of the tetramer upon SDS-PAGE
I47T
InhA mutation that occur in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis, show unimpaired inhibition by triclosan, with uncompetitive inhibition constant
I47T
similar to wild-type InhA, cross-linking of the isoniazid resistant mutant gives three bands on SDS-PAGE assigned to monomer, dimer, and tetrameric forms of the protein. The inhibition of the enzyme with the isoniazid-NAD adduct results in loss of the band assigned to tetramer. In contrast, cross-linking in the presence of saturating concentrations of NADH yields a lower amount of the tetramer upon SDS-PAGE
S94A
isoniazid-resistant mutant, alteration in the binding network involving a conserved water molecule and O9 atom of molecule of NADH leads to increase of the flexibility of the conserved water molecule and decrease of the affinity of NADH by protein
S94A
similar to wild-type InhA, cross-linking of the isoniazid resistant mutant gives three bands on SDS-PAGE assigned to monomer, dimer, and tetrameric forms of the protein. The inhibition of the enzyme with the isoniazid-NAD adduct results in loss of the band assigned to tetramer. In contrast, cross-linking in the presence of saturating concentrations of NADH yields a lower amount of the tetramer upon SDS-PAGE
Y158F
decreased Kcat, unaffected Km for trans-2-dodecenoyl-CoA, lower Km for NADH
Y158F
mutation reduces the affinity of triclosan for the enzyme and results in noncompetitive inhibition
Y158F
mutant retains only 1.8% of the wild-type kcat with a 2fold increase of the Km for octenoyl-CoA. Residue Y158 is essential for stereospecificity of protonation, the mutant accumulates a covalent adduct between crotonyl-CoA and NADH
Y158S
strong decrease in kcat to only 0.16% of wild-type activity
I21V
-
isoniazid resistance mutant of Mycobacterium tuberculosis enoyl-[acyl-carrier-protein] reductase
I21V
-
mutant, studied for understanding of the isoniazid drug resistance mechanism
I47T
-
mutant, studied for understanding of the isoniazid drug resistance mechanism
S94A
-
mutant, studied for understanding of the isoniazid drug resistance mechanism
S94A
-
similar activity compared to wild-type but a reduced NADH affinity, the affinity of S94A for is also decreased
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni-NTA agarose column chromatography, and Superdex 200 gel filtration
nickel-chelated His-Trap column chromatography, and Superdex 200 gel filtration
recombinant His-tagged InhA from Escherichia coli BL21(DE3) by nickel affinity chromatography and gel filtration
using a 15Q high-resolution anion exchange column and a Hightrap butyl Sepharose column
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed with N-terminal hexa-histidine motifs in Escherichia coli BL21 (DE3) pLysS cells
expression of His-tagged InhA in Escherichia coli BL21(DE3)
into a pET15b vector for expression in Escherichia coli BL21-Gold (DE3)
the inhA gene was cloned into the pMK1 mycobacterial expression vector under the control of the strong promoter hsp60. The resulting construct is used to transform Mycobacterium bovis BCG Pasteur in order to allow over-production of recombinant His-tagged InhA
expression Saccharomyces cerevisiae etr1D cells lacking Etr1p, the 2-trans-enoyl-thioester reductase of mitochondrial type 2 fatty acid synthase. Yeast mitochondria are used as a surrogate compartment for hosting the drug-target protein InhA from mycobacterial FASII. The heterologous enzyme is ectopically expressed in a yeast mutant strain from which the native gene encoding the corresponding mitochondrial FASII enzyme is missing. Using an appropriate fungal mitochondrial leader sequence, the mycobacterial protein is directed to the mitochondria, where it can rescue the respiratory growth phenotype of the mutant. The rationale behind the assay is that added antimycolates are foreseen to inhibit the mycobacterial enzyme, thereby recreating the respiratory deficiency of the original mutant, discernible as poor colony formation and growth on glycerol medium
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
InhA is an attractive target for the development of drugs against tuberculosis
medicine
pharmacology
medicine
medicine
tuberculosis, TB, target of anti-tubercular agents
medicine
Mycobacterium tuberculosis enoyl acyl carrier protein reductase represents a prospective drug target against tuberculosis, identified MtENR binders can be characterized as potential therapeutic targets laying a foundation for future lead identification and optimization studies
medicine
the results can be of primary importance in to elucidate the mechanism of action of isoniazid and to better understand the isoniazid-dependent resistances, and they can also prove useful in the design of a new generation of antitubercular drugs
medicine
WYW is a potential lead compound for the development of new anti-tuberculosis drugs
medicine
the enzyme is a target for development of anti-tuberculosis drugs
pharmacology
the enzyme is a target for developing novel anti-tubercular agents
pharmacology
the enzyme is a target for the antitubercular drug isoniazid. InhA inhibitors targeted at the enoyl substrate binding site may be effective against existing isoniazid-resistant strains of Mycobacterium tuberculosis
medicine
-
tuberculosis, TB, target of anti-tubercular agents
medicine
-
enoyl-acyl carrier protein reductase inhibitors turn out to be clinically useful antimicrobials
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Basso, L.A.; Zheng, R.; Musser, J.M.; Jacobs, W.R., Jr.; Blanchard, J.S.
Mechanisms of isoniazid resistance in Mycobacterium tuberculosis: enzymic characterization of enoyl reductase mutants identified in isoniazid-resistant clinical isolates
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178
769-775
1998
Mycobacterium tuberculosis
Parikh, S.; Moynihan, D.P.; Xiao, G.; Tonge, P.J.
Roles of tyrosine 158 and lysine 165 in the catalytic mechanism of InhA, the enoyl-ACP reductase from Mycobacterium tuberculosis
Biochemistry
38
13623-13634
1999
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis H37Rv (P9WGR1)
Oliveira, J.S.; Sousa, E.H.; Basso, L.A.; Palaci, M.; Dietze, R.; Santos, D.S.; Moreira, I.S.
An inorganic iron complex that inhibits wild-type and an isoniazid-resistant mutant 2-trans-enoyl-ACP (CoA) reductase from Mycobacterium tuberculosis
Chem. Commun. (Camb.)
2004
312-313
2004
Mycobacterium tuberculosis
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Schroeder, E.K.; Basso, L.A.; Santos, D.S.; de Souza, O.N.
Molecular dynamics simulation studies of the wild-type, I21V, and I16T mutants of isoniazid-resistant Mycobacterium tuberculosis enoyl reductase (InhA) in complex with NADH: toward the understanding of NADH-InhA different affinities
Biophys. J.
89
876-884
2005
Mycobacterium tuberculosis
Oliveira, J.S.; de Sousa, E.H.; de Souza, O.N.; Moreira, I.S.; Santos, D.S.; Basso, L.A.
Slow-onset inhibition of 2-trans-enoyl-ACP (CoA) reductase from Mycobacterium tuberculosis by an inorganic complex
Curr. Pharm. Des.
12
2409-2424
2006
Mycobacterium tuberculosis
He, X.; Alian, A.; Stroud, R.; Ortiz de Montellano, P.R.
Pyrrolidine carboxamides as a novel class of inhibitors of enoyl acyl carrier protein reductase from Mycobacterium tuberculosis
J. Med. Chem.
49
6308-6323
2006
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv (P9WGR1)
Oliveira, J.S.; Pereira, J.H.; Canduri, F.; Rodrigues, N.C.; de Souza, O.N.; de Azevedo, W.F.; Basso, L.A.; Santos, D.S.
Crystallographic and pre-steady-state kinetics studies on binding of NADH to wild-type and isoniazid-resistant enoyl-ACP(CoA) reductase enzymes from Mycobacterium tuberculosis
J. Mol. Biol.
359
646-666
2006
Mycobacterium tuberculosis
Lu, H.; Tonge, P.J.
Inhibitors of FabI, an enzyme drug target in the bacterial fatty acid biosynthesis pathway
Acc. Chem. Res.
41
11-20
2008
Mycobacterium tuberculosis
Sharma, S.K.; Kumar, G.; Kapoor, M.; Surolia, A.
Combined effect of epigallocatechin gallate and triclosan on enoyl-ACP reductase of Mycobacterium tuberculosis
Biochem. Biophys. Res. Commun.
368
12-17
2008
Mycobacterium tuberculosis
Bonnac, L.; Gao, G.Y.; Chen, L.; Felczak, K.; Bennett, E.M.; Xu, H.; Kim, T.; Liu, N.; Oh, H.; Tonge, P.J.; Pankiewicz, K.W.
Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis
Bioorg. Med. Chem. Lett.
17
4588-4591
2007
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv (P9WGR1)
Kumar, A.; Siddiqi, M.I.
CoMFA based de novo design of pyrrolidine carboxamides as inhibitors of enoyl acyl carrier protein reductase from Mycobacterium tuberculosis
J. Mol. Model.
14
923-935
2008
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv (P9WGR1)
Dias, M.V.; Vasconcelos, I.B.; Prado, A.M.; Fadel, V.; Basso, L.A.; de Azevedo, W.F.; Santos, D.S.
Crystallographic studies on the binding of isonicotinyl-NAD adduct to wild-type and isoniazid resistant 2-trans-enoyl-ACP (CoA) reductase from Mycobacterium tuberculosis
J. Struct. Biol.
159
369-380
2007
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv (P9WGR1)
Karioti, A.; Skaltsa, H.; Zhang, X.; Tonge, P.J.; Perozzo, R.; Kaiser, M.; Franzblau, S.G.; Tasdemir, D.
Inhibiting enoyl-ACP reductase (FabI) across pathogenic microorganisms by linear sesquiterpene lactones from Anthemis auriculata
Phytomedicine
15
1125-1129
2008
Escherichia coli, Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv, Plasmodium falciparum
Massengo-Tiasse, R.P.; Cronan, J.E.
Diversity in enoyl-acyl carrier protein reductases
Cell. Mol. Life Sci.
66
1507-1517
2009
Escherichia coli, Mycobacterium tuberculosis
Subba Rao, G.; Vijayakrishnan, R.; Kumar, M.
Structure-based design of a novel class of potent inhibitors of InhA, the enoyl acyl carrier protein reductase from Mycobacterium tuberculosis: a computer modelling approach
Chem. Biol. Drug Des.
72
444-449
2008
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv (P9WGR1)
Stigliani, J.L.; Arnaud, P.; Delaine, T.; Bernardes-Genisson, V.; Meunier, B.; Bernadou, J.
Binding of the tautomeric forms of isoniazid-NAD adducts to the active site of the Mycobacterium tuberculosis enoyl-ACP reductase (InhA): a theoretical approach
J. Mol. Graph. Model.
27
536-545
2008
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis H37Rv (P9WGR1)
Kumar, A.; Siddiqi, M.I.
Receptor based 3D-QSAR to identify putative binders of Mycobacterium tuberculosis enoyl acyl carrier protein reductase
J. Mol. Model.
16
877-893
2010
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv (P9WGR1)
Luckner, S.R.; Liu, N.; am Ende, C.W.; Tonge, P.J.; Kisker, C.
A slow, tight binding inhibitor of InhA, the enoyl-acyl carrier protein reductase from Mycobacterium tuberculosis
J. Biol. Chem.
285
14330-14337
2010
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis H37Rv (P9WGR1)
Deraeve, C.; Dorobantu, I.M.; Rebbah, F.; Le Quemener, F.; Constant, P.; Quemard, A.; Bernardes-Genisson, V.; Bernadou, J.; Pratviel, G.
Chemical synthesis, biological evaluation and structure-activity relationship analysis of azaisoindolinones, a novel class of direct enoyl-ACP reductase inhibitors as potential antimycobacterial agents
Bioorg. Med. Chem.
19
6225-6232
2011
Mycobacterium tuberculosis
Kwon, Y.J.; Sohn, M.J.; Oh, T.; Cho, S.N.; Kim, C.J.; Kim, W.G.
Panosialins, inhibitors of enoyl-ACP reductase from Streptomyces sp. AN1761
J. Microbiol. Biotechnol.
23
184-188
2013
Streptococcus pneumoniae, Mycobacterium tuberculosis
da Costa, A.L.; Pauli, I.; Dorn, M.; Schroeder, E.K.; Zhan, C.G.; de Souza, O.N.
Conformational changes in 2-trans-enoyl-ACP (CoA) reductase (InhA) from M. tuberculosis induced by an inorganic complex: a molecular dynamics simulation study
J. Mol. Model.
18
1779-1790
2012
Mycobacterium tuberculosis
Ghattas, M.A.; Mansour, R.A.; Atatreh, N.; Bryce, R.A.
Analysis of enoyl-acyl carrier protein reductase structure and interactions yields an efficient virtual screening approach and suggests a potential allosteric site
Chem. Biol. Drug Des.
87
131-142
2016
Escherichia coli, Plasmodium falciparum, Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis H37Rv (P9WGR1)
Stec, J.; Vilcheze, C.; Lun, S.; Perryman, A.L.; Wang, X.; Freundlich, J.S.; Bishai, W.; Jacobs, W.R.; Kozikowski, A.P.
Biological evaluation of potent triclosan-derived inhibitors of the enoyl-acyl carrier protein reductase InhA in drug-sensitive and drug-resistant strains of Mycobacterium tuberculosis
ChemMedChem
9
2528-2537
2014
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
Sink, R.; Sosic, I.; Zivec, M.; Fernandez-Menendez, R.; Turk, S.; Pajk, S.; Alvarez-Gomez, D.; Lopez-Roman, E.M.; Gonzales-Cortez, C.; Rullas-Triconado, J.; Angulo-Barturen, I.; Barros, D.; Ballell-Pages, L.; Young, R.J.; Encinas, L.; Gobec, S.
Design, synthesis, and evaluation of new thiadiazole-based direct inhibitors of enoyl acyl carrier protein reductase (InhA) for the treatment of tuberculosis
J. Med. Chem.
58
613-624
2015
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
Chollet, A.; Mourey, L.; Lherbet, C.; Delbot, A.; Julien, S.; Baltas, M.; Bernadou, J.; Pratviel, G.; Maveyraud, L.; Bernardes-Genisson, V.
Crystal structure of the enoyl-ACP reductase of Mycobacterium tuberculosis (InhA) in the apo-form and in complex with the active metabolite of isoniazid pre-formed by a biomimetic approach
J. Struct. Biol.
190
328-337
2015
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis H37Rv (P9WGR1)
Owono Owono, L.C.; Ntie-Kang, F.; Keita, M.; Megnassan, E.; Frecer, V.; Miertus, S.
Virtually designed triclosan-based inhibitors of enoyl-acyl carrier protein reductase of Mycobacterium tuberculosis and of Plasmodium falciparum
Mol. Inform.
34
292-307
2015
Mycobacterium tuberculosis, Plasmodium falciparum
Martinelli, L.K.B.; Rotta, M.; Villela, A.D.; Rodrigues-Junior, V.S.; Abbadi, B.L.; Trindade, R.V.; Petersen, G.O.; Danesi, G.M.; Nery, L.R.; Pauli, I.; Campos, M.M.; Bonan, C.D.; de Souza, O.N.; Basso, L.A.; Santos, D.S.
Functional, thermodynamics, structural and biological studies of in silico-identified inhibitors of Mycobacterium tuberculosis enoyl-ACP(CoA) reductase enzyme
Sci. Rep.
7
46696
2017
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
Parikh, S.; Xiao, G.; Tonge, P.
Inhibition of InhA, the enoyl reductase from Mycobacterium tuberculosis, by triclosan and isoniazid
Biochemistry
39
7645-7650
2000
Mycolicibacterium smegmatis (P42829), Mycobacterium tuberculosis (P9WGR1), Mycolicibacterium smegmatis ATCC 700084 (P42829), Mycobacterium tuberculosis ATCC 25618 (P9WGR1)
He, X.; Alian, A.; Ortiz de Montellano, P.
Inhibition of the Mycobacterium tuberculosis enoyl acyl carrier protein reductase InhA by arylamides
Bioorg. Med. Chem.
15
6649-6658
2007
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis, Mycobacterium tuberculosis ATCC 25618 (P9WGR1)
Schroeder, E.; Basso, L.; Santos, D.; De Souza, O.
Molecular dynamics simulation studies of the wild-type, I21V, and I16T mutants of isoniazid-resistant Mycobacterium tuberculosis enoyl reductase (InhA) in complex with NADH Toward the understanding of NADH-InhA different affinities
Biophys. J.
89
876-884
2005
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis ATCC 25618 (P9WGR1)
Subba Rao, G.; Vijayakrishnan, R.; Kumar, M.
Structure-based design of a novel class of potent inhibitors of InhA, the enoyl acyl carrier protein reductase from Mycobacterium tuberculosis A computer modelling approach
Chem. Biol. Drug Des.
72
444-449
2008
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis, Mycobacterium tuberculosis ATCC 25618 (P9WGR1)
Nguyen, M.; Quemard, A.; Marrakchi, H.; Bernadou, J.; Meunier, B.
The nonenzymatic activation of isoniazid by MnIII-pyrophosphate in the presence of NADH produces the inhibition of the enoyl-ACP reductase InhA from Mycobacterium tuberculosis
Chemistry
4
35-40
2001
Mycobacterium tuberculosis
-
Guardia, A.; Gulten, G.; Fernandez, R.; Gomez, J.; Wang, F.; Convery, M.; Blanco, D.; Martinez, M.; Perez-Herran, E.; Alonso, M.; Ortega, F.; Rullas, J.; Calvo, D.; Mata, L.; Young, R.; Sacchettini, J.; Mendoza-Losana, A.; Remuinan, M.
N-Benzyl-4-((heteroaryl)methyl)benzamides a new class of direct NADH-dependent 2-trans enoyl-acyl carrier protein reductase (InhA) inhibitors with antitubercular activity
ChemMedChem
11
687-701
2016
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis ATCC 25618 (P9WGR1)
Pedgaonkar, G.; Sridevi, J.; Jeankumar, V.; Saxena, S.; Devi, P.; Renuka, J.; Yogeeswari, P.; Sriram, D.
Development of 2-(4-oxoquinazolin-3(4H)-yl)acetamide derivatives as novel enoyl-acyl carrier protein reductase (InhA) inhibitors for the treatment of tuberculosis
Eur. J. Med. Chem.
86
613-627
2014
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis, Mycobacterium tuberculosis ATCC 25618 (P9WGR1)
Rotta, M.; Pissinate, K.; Villela, A.; Back, D.; Timmers, L.; Bachega, J.; De Souza, O.; Santos, D.; Basso, L.; Machado, P.
Piperazine derivatives Synthesis, inhibition of the Mycobacterium tuberculosis enoyl-acyl carrier protein reductase and SAR studies
Eur. J. Med. Chem.
90
436-447
2015
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis, Mycobacterium tuberculosis ATCC 25618 (P9WGR1)
Luckner, S.; Liu, N.; Am Ende, C.; Tonge, P.; Kisker, C.
A slow, tight binding inhibitor of InhA, the enoyl-acyl carrier protein reductase from Mycobacterium tuberculosis
J. Biol. Chem.
285
14330-14337
2010
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis ATCC 25618 (P9WGR1)
Vasconcelos, I.; Basso, L.; Santos, D.
Kinetic and equilibrium mechanisms of substrate binding to Mycobacterium tuberculosis enoyl reductase Implications to function-based antitubercular agent design
J. Braz. Chem. Soc.
21
1503-1508
2010
Mycobacterium tuberculosis
-
Da Costa, A.; Pauli, I.; Dorn, M.; Schroeder, E.; Zhan, C.; De Souza, O.
Conformational changes in 2-trans-enoyl-ACP (CoA) reductase (InhA) from M. tuberculosis induced by an inorganic complex A molecular dynamics simulation study
J. Mol. Model.
18
1779-1790
2012
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis, Mycobacterium tuberculosis ATCC 25618 (P9WGR1)
Gurvitz, A.
Triclosan inhibition of mycobacterial InhA in Saccharomyces cerevisiae Yeast mitochondria as a novel platform for in vivo antimycolate assays
Lett. Appl. Microbiol.
50
399-405
2010
Mycobacterium tuberculosis
Xia, Y.; Zhou, Y.; Carter, D.; McNeil, M.; Choi, W.; Halladay, J.; Berry, P.; Mao, W.; Hernandez, V.; O'Malley, T.; Korkegian, A.; Sunde, B.; Flint, L.; Woolhiser, L.; Scherman, M.; Gruppo, V.; Hastings, C.; Robertson, G.; Ioerger, T.; Sacchettini, J.
Discovery of a cofactor-independent inhibitor of Mycobacterium tuberculosis InhA
Life Sci. Alliance
1
e201800025
2018
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis ATCC 25618 (P9WGR1)
Molle, V.; Gulten, G.; Vilcheze, C.; Veyron-Churlet, R.; Zanella-Cleon, I.; Sacchettini, J.; Jacobs Jr, W.; Kremer, L.
Phosphorylation of InhA inhibits mycolic acid biosynthesis and growth of Mycobacterium tuberculosis
Mol. Microbiol.
78
1591-1605
2010
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis ATCC 25618 (P9WGR1)
Kruh, N.; Rawat, R.; Ruzsicska, B.; Tonge, P.
Probing mechanisms of resistance to the tuberculosis drug isoniazid Conformational changes caused by inhibition of InhA, the enoyl reductase from Mycobacterium tuberculosis
Protein Sci.
16
1617-1627
2007
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis ATCC 25618 (P9WGR1)
Voegeli, B.; Rosenthal, R.G.; Stoffel, G.M.M.; Wagner, T.; Kiefer, P.; Cortina, N.S.; Shima, S.; Erb, T.J.
InhA, the enoyl-thioester reductase from Mycobacterium tuberculosis forms a covalent adduct during catalysis
J. Biol. Chem.
293
17200-17207
2018
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis H37Rv (P9WGR1)
Mahfuz, A.; Stambuk Opazo, F.; Aguilar, L.; Iqbal, M.
Carfilzomib as a potential inhibitor of NADH-dependent enoyl-acyl carrier protein reductases of Klebsiella pneumoniae and Mycobacterium tuberculosis as a drug target enzyme insights from molecular docking and molecular dynamics
J. Biomol. Struct. Dyn.
30
1-17
2020
Klebsiella pneumoniae (A0A0G3SXJ0), Klebsiella pneumoniae (W9BFS8), Klebsiella pneumoniae, Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis, Mycobacterium tuberculosis ATCC 25618 (P9WGR1)
Lone, M.Y.; Athar, M.; Gupta, V.K.; Jha, P.C.
Identification of Mycobacterium tuberculosis enoyl-acyl carrier protein reductase inhibitors A combined in-silico and in-vitro analysis
J. Mol. Graph. Model.
76
172-180
2017
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv (P9WGR1)
Shaw, D.J.; Robb, K.; Vetter, B.V.; Tong, M.; Molle, V.; Hunt, N.T.; Hoskisson, P.A.
Disruption of key NADH-binding pocket residues of the Mycobacterium tuberculosis InhA affects DD-CoA binding ability
Sci. Rep.
7
4714
2017
Mycobacterium tuberculosis
Prasad, M.S.; Bhole, R.P.; Khedekar, P.B.; Chikhale, R.V.
Mycobacterium enoyl acyl carrier protein reductase (InhA) A key target for antitubercular drug discovery
Bioorg. Chem.
115
105242
2021
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis H37Rv (P9WGR1)
Joshi, S.D.; More, U.A.; Dixit, S.R.; Balmi, S.V.; Kulkarni, B.G.; Ullagaddi, G.; Lherbet, C.; Aminabhavi, T.M.
Chemical synthesis and in silico molecular modeling of novel pyrrolyl benzohydrazide derivatives Their biological evaluation against enoyl ACP reductase (InhA) and Mycobacterium tuberculosis
Bioorg. Chem.
75
181-200
2017
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv (P9WGR1), Mycobacterium tuberculosis H37Rv
Rodriguez, F.; Saffon, N.; Sammartino, J.; Degiacomi, G.; Pasca, M.; Lherbet, C.
First triclosan-based macrocyclic inhibitors of InhA enzyme
Bioorg. Chem.
95
103498
2020
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis H37Rv (P9WGR1)
de Avila, M.B.; Bitencourt-Ferreira, G.; de Azevedo, W.F.
Structural basis for inhibition of enoyl-[acyl carrier protein] reductase (InhA) from Mycobacterium tuberculosis
Curr. Med. Chem.
27
745-759
2020
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis
Dogan, H.; Dogan, S.D.; Guenduez, M.G.; Krishna, V.S.; Lherbet, C.; Sriram, D.; Sahin, O.; Saripinar, E.
Discovery of hydrazone containing thiadiazoles as Mycobacterium tuberculosis growth and enoyl acyl carrier protein reductase (InhA) inhibitors
Eur. J. Med. Chem.
188
112035
2020
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
Dogan, S.D.; Guenduez, M.G.; Dogan, H.; Krishna, V.S.; Lherbet, C.; Sriram, D.
Design and synthesis of thiourea-based derivatives as Mycobacterium tuberculosis growth and enoyl acyl carrier protein reductase (InhA) inhibitors
Eur. J. Med. Chem.
199
112402
2020
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv (P9WGR1)
Pflegr, V.; Horvath, L.; Stolariova, J.; Pal, A.; Kordulakova, J.; Bosze, S.; Vinsova, J.; Kratky, M.
Design and synthesis of 2-(2-isonicotinoylhydrazineylidene)propanamides as InhA inhibitors with high antitubercular activity
Eur. J. Med. Chem.
223
113668
2021
Mycobacterium avium, Mycobacterium avium 330/88, Mycobacterium kansasii, Mycobacterium kansasii 235/80, Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
Jayaraman, M.; Ramadas, K.
An integrated computational investigation to unveil the structural impacts of mutation on the InhA structural gene of Mycobacterium tuberculosis
J. Mol. Graph. Model.
101
107768
2020
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis H37Rv (P9WGR1)
Khan, A.M.; Shawon, J.; Halim, M.A.
Multiple receptor conformers based molecular docking study of fluorine enhanced ethionamide with Mycobacterium enoyl ACP reductase (InhA)
J. Mol. Graph. Model.
77
386-398
2017
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis H37Rv (P9WGR1)
Joshi, S.; Kumar, S.; Patil, S.; Vijayakumar, M.; Kulkarni, V.; Nadagouda, M.; Badiger, A.; Lherbet, C.; Aminabhavi, T.
Chemical synthesis, molecular modeling and pharmacophore mapping of new pyrrole derivatives as inhibitors of InhA enzyme and Mycobacterium tuberculosis growth
Med. Chem. Res.
28
1838-1863
2019
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis H37Rv (P9WGR1)
-
Pinzi, L.; Lherbet, C.; Baltas, M.; Pellati, F.; Rastelli, G.
In silico repositioning of cannabigerol as a novel inhibitor of the enoyl acyl carrier protein (ACP) reductase (InhA)
Molecules
24
2567
2019
Mycobacterium tuberculosis (P9WGR1), Mycobacterium tuberculosis H37Rv (P9WGR1)
Unissa, A.; Dusthackeer, V.; Kumar, M.; Nagarajan, P.; Sukumar, S.; Kumari, V.; Lakshmi, A.; Hanna, L.
Variants of katG, inhA and nat genes are not associated with mutations in efflux pump genes (mmpL3 and mmpL7) in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis from India
Tuberculosis
107
144-148
2017
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
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