BRENDA - Enzyme Database
show all sequences of 1.14.13.70

An overview of azoles targeting sterol 14?-demethylase for antileishmanial therapy

Emami, S.; Tavangar, P.; Keighobadi, M.; Eur. J. Med. Chem. 135, 241-259 (2017)

Data extracted from this reference:

Application
Application
Commentary
Organism
medicine
the chemotherapy of leishmaniasis is a serious problem in the field of neglected tropical diseases. Since the biosynthesis of specific sterols is vital for effective survival, normal proliferation and infectivity of Leishmania parasites, the sterol 14alpha-demethylase inhibitors obtained from azole antifungal drug discovery programs can be used in antileishmanial therapy
Leishmania mexicana
medicine
the chemotherapy of leishmaniasis is a serious problem in the field of neglected tropical diseases. Since the biosynthesis of specific sterols is vital for effective survival, normal proliferation and infectivity of Leishmania parasites, the sterol 14alpha-demethylase inhibitors obtained from azole antifungal drug discovery programs can be used in antileishmanial therapy
Leishmania major
medicine
the chemotherapy of leishmaniasis is a serious problem in the field of neglected tropical diseases. Since the biosynthesis of specific sterols is vital for effective survival, normal proliferation and infectivity of Leishmania parasites, the sterol 14alpha-demethylase inhibitors obtained from azole antifungal drug discovery programs can be used in antileishmanial therapy
Leishmania infantum
pharmacology
the chemotherapy of leishmaniasis is a serious problem in the field of neglected tropical diseases. Since the biosynthesis of specific sterols is vital for effective survival, normal proliferation and infectivity of Leishmania parasites, the sterol 14alpha-demethylase inhibitors obtained from azole antifungal drug discovery programs can be used in antileishmanial therapy
Leishmania mexicana
pharmacology
the chemotherapy of leishmaniasis is a serious problem in the field of neglected tropical diseases. Since the biosynthesis of specific sterols is vital for effective survival, normal proliferation and infectivity of Leishmania parasites, the sterol 14alpha-demethylase inhibitors obtained from azole antifungal drug discovery programs can be used in antileishmanial therapy
Leishmania major
pharmacology
the chemotherapy of leishmaniasis is a serious problem in the field of neglected tropical diseases. Since the biosynthesis of specific sterols is vital for effective survival, normal proliferation and infectivity of Leishmania parasites, the sterol 14alpha-demethylase inhibitors obtained from azole antifungal drug discovery programs can be used in antileishmanial therapy
Leishmania infantum
Inhibitors
Inhibitors
Commentary
Organism
Structure
2,2-dimethyl-1,3-dichloropropane
i.e.D0870
Leishmania infantum
2,2-dimethyl-1,3-dichloropropane
i.e.D0870
Leishmania major
2,2-dimethyl-1,3-dichloropropane
i.e.D0870
Leishmania mexicana
3-(alpha-imidazolylbenzyl)indole
-
Leishmania infantum
3-(alpha-imidazolylbenzyl)indole
-
Leishmania major
3-(alpha-imidazolylbenzyl)indole
-
Leishmania mexicana
3-(alpha-triazolylbenzyl)indole
-
Leishmania infantum
3-(alpha-triazolylbenzyl)indole
-
Leishmania major
3-(alpha-triazolylbenzyl)indole
-
Leishmania mexicana
bifonazole
-
Leishmania infantum
bifonazole
-
Leishmania major
bifonazole
-
Leishmania mexicana
clotrimazole
-
Leishmania infantum
clotrimazole
-
Leishmania major
clotrimazole
-
Leishmania mexicana
econazole
-
Leishmania infantum
econazole
-
Leishmania major
econazole
-
Leishmania mexicana
fluconazole
-
Leishmania infantum
fluconazole
-
Leishmania major
fluconazole
-
Leishmania mexicana
itraconazole
-
Leishmania infantum
itraconazole
-
Leishmania major
itraconazole
-
Leishmania mexicana
ketoconazole
-
Leishmania infantum
ketoconazole
-
Leishmania major
ketoconazole
-
Leishmania mexicana
meglumine antimoniate
-
Leishmania infantum
meglumine antimoniate
-
Leishmania major
meglumine antimoniate
-
Leishmania mexicana
miconazole
-
Leishmania infantum
miconazole
-
Leishmania major
miconazole
-
Leishmania mexicana
posaconazole
-
Leishmania infantum
posaconazole
-
Leishmania major
posaconazole
-
Leishmania mexicana
voriconazole
-
Leishmania infantum
voriconazole
-
Leishmania major
voriconazole
-
Leishmania mexicana
Organism
Organism
UniProt
Commentary
Textmining
Leishmania infantum
A2TEF2
-
-
Leishmania major
-
-
-
Leishmania mexicana
-
-
-
Source Tissue
Source Tissue
Commentary
Organism
Textmining
amastigote
-
Leishmania mexicana
-
amastigote
-
Leishmania major
-
amastigote
-
Leishmania infantum
-
promastigote
-
Leishmania mexicana
-
promastigote
-
Leishmania major
-
promastigote
-
Leishmania infantum
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
Substrate Product ID
14alpha-methylzymosterol + NADPH + H+ + O2
-
744843
Leishmania mexicana
?
-
-
-
?
14alpha-methylzymosterol + NADPH + H+ + O2
-
744843
Leishmania infantum
?
-
-
-
?
lanosterol + NADPH + H+ + O2
-
744843
Leishmania mexicana
?
-
-
-
?
lanosterol + NADPH + H+ + O2
-
744843
Leishmania infantum
?
-
-
-
?
obtusifoliol + NADPH + H+ + O2
-
744843
Leishmania mexicana
?
-
-
-
?
obtusifoliol + NADPH + H+ + O2
-
744843
Leishmania infantum
?
-
-
-
?
IC50 Value
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
0.00281
-
pH and temperature not specified in the publication
Leishmania infantum
clotrimazole
0.0044
-
pH and temperature not specified in the publication, axenic amastigotes
Leishmania mexicana
3-(alpha-imidazolylbenzyl)indole
0.00536
-
pH and temperature not specified in the publication
Leishmania infantum
econazole
0.00897
-
pH and temperature not specified in the publication
Leishmania infantum
bifonazole
Application (protein specific)
Application
Commentary
Organism
medicine
the chemotherapy of leishmaniasis is a serious problem in the field of neglected tropical diseases. Since the biosynthesis of specific sterols is vital for effective survival, normal proliferation and infectivity of Leishmania parasites, the sterol 14alpha-demethylase inhibitors obtained from azole antifungal drug discovery programs can be used in antileishmanial therapy
Leishmania mexicana
medicine
the chemotherapy of leishmaniasis is a serious problem in the field of neglected tropical diseases. Since the biosynthesis of specific sterols is vital for effective survival, normal proliferation and infectivity of Leishmania parasites, the sterol 14alpha-demethylase inhibitors obtained from azole antifungal drug discovery programs can be used in antileishmanial therapy
Leishmania major
medicine
the chemotherapy of leishmaniasis is a serious problem in the field of neglected tropical diseases. Since the biosynthesis of specific sterols is vital for effective survival, normal proliferation and infectivity of Leishmania parasites, the sterol 14alpha-demethylase inhibitors obtained from azole antifungal drug discovery programs can be used in antileishmanial therapy
Leishmania infantum
pharmacology
the chemotherapy of leishmaniasis is a serious problem in the field of neglected tropical diseases. Since the biosynthesis of specific sterols is vital for effective survival, normal proliferation and infectivity of Leishmania parasites, the sterol 14alpha-demethylase inhibitors obtained from azole antifungal drug discovery programs can be used in antileishmanial therapy
Leishmania mexicana
pharmacology
the chemotherapy of leishmaniasis is a serious problem in the field of neglected tropical diseases. Since the biosynthesis of specific sterols is vital for effective survival, normal proliferation and infectivity of Leishmania parasites, the sterol 14alpha-demethylase inhibitors obtained from azole antifungal drug discovery programs can be used in antileishmanial therapy
Leishmania major
pharmacology
the chemotherapy of leishmaniasis is a serious problem in the field of neglected tropical diseases. Since the biosynthesis of specific sterols is vital for effective survival, normal proliferation and infectivity of Leishmania parasites, the sterol 14alpha-demethylase inhibitors obtained from azole antifungal drug discovery programs can be used in antileishmanial therapy
Leishmania infantum
IC50 Value (protein specific)
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
0.00281
-
pH and temperature not specified in the publication
Leishmania infantum
clotrimazole
0.0044
-
pH and temperature not specified in the publication, axenic amastigotes
Leishmania mexicana
3-(alpha-imidazolylbenzyl)indole
0.00536
-
pH and temperature not specified in the publication
Leishmania infantum
econazole
0.00897
-
pH and temperature not specified in the publication
Leishmania infantum
bifonazole
Inhibitors (protein specific)
Inhibitors
Commentary
Organism
Structure
2,2-dimethyl-1,3-dichloropropane
i.e.D0870
Leishmania mexicana
2,2-dimethyl-1,3-dichloropropane
i.e.D0870
Leishmania major
2,2-dimethyl-1,3-dichloropropane
i.e.D0870
Leishmania infantum
3-(alpha-imidazolylbenzyl)indole
-
Leishmania mexicana
3-(alpha-imidazolylbenzyl)indole
-
Leishmania major
3-(alpha-imidazolylbenzyl)indole
-
Leishmania infantum
3-(alpha-triazolylbenzyl)indole
-
Leishmania mexicana
3-(alpha-triazolylbenzyl)indole
-
Leishmania major
3-(alpha-triazolylbenzyl)indole
-
Leishmania infantum
bifonazole
-
Leishmania mexicana
bifonazole
-
Leishmania major
bifonazole
-
Leishmania infantum
clotrimazole
-
Leishmania mexicana
clotrimazole
-
Leishmania major
clotrimazole
-
Leishmania infantum
econazole
-
Leishmania mexicana
econazole
-
Leishmania major
econazole
-
Leishmania infantum
fluconazole
-
Leishmania mexicana
fluconazole
-
Leishmania major
fluconazole
-
Leishmania infantum
itraconazole
-
Leishmania mexicana
itraconazole
-
Leishmania major
itraconazole
-
Leishmania infantum
ketoconazole
-
Leishmania mexicana
ketoconazole
-
Leishmania major
ketoconazole
-
Leishmania infantum
meglumine antimoniate
-
Leishmania mexicana
meglumine antimoniate
-
Leishmania major
meglumine antimoniate
-
Leishmania infantum
miconazole
-
Leishmania mexicana
miconazole
-
Leishmania major
miconazole
-
Leishmania infantum
posaconazole
-
Leishmania mexicana
posaconazole
-
Leishmania major
posaconazole
-
Leishmania infantum
voriconazole
-
Leishmania mexicana
voriconazole
-
Leishmania major
voriconazole
-
Leishmania infantum
Source Tissue (protein specific)
Source Tissue
Commentary
Organism
Textmining
amastigote
-
Leishmania mexicana
-
amastigote
-
Leishmania major
-
amastigote
-
Leishmania infantum
-
promastigote
-
Leishmania mexicana
-
promastigote
-
Leishmania major
-
promastigote
-
Leishmania infantum
-
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
ID
14alpha-methylzymosterol + NADPH + H+ + O2
-
744843
Leishmania mexicana
?
-
-
-
?
14alpha-methylzymosterol + NADPH + H+ + O2
-
744843
Leishmania infantum
?
-
-
-
?
lanosterol + NADPH + H+ + O2
-
744843
Leishmania mexicana
?
-
-
-
?
lanosterol + NADPH + H+ + O2
-
744843
Leishmania infantum
?
-
-
-
?
obtusifoliol + NADPH + H+ + O2
-
744843
Leishmania mexicana
?
-
-
-
?
obtusifoliol + NADPH + H+ + O2
-
744843
Leishmania infantum
?
-
-
-
?
General Information
General Information
Commentary
Organism
malfunction
inactivation of the enzyme in promastigotes results in disruption of the membrane stability, increase of membrane fluidity, failure to maintain lipid rafts, and hypersensitivity to heat stress along with altered morphology and cytokinesis defect. The effect deletion on lipid composition and sterol biosynthesis is a complete loss of ergostane-based sterols (5-dehydroepisterol, ergosterol, and episterol) and accumulation of toxic 14-methylated sterols
Leishmania mexicana
malfunction
inactivation of the enzyme in promastigotes results in disruption of the membrane stability, increase of membrane fluidity, failure to maintain lipid rafts, and hypersensitivity to heat stress along with altered morphology and cytokinesis defect. The effect deletion on lipid composition and sterol biosynthesis is a complete loss of ergostane-based sterols (5-dehydroepisterol, ergosterol, and episterol) and accumulation of toxic 14-methylated sterols
Leishmania major
malfunction
inactivation of the enzyme in promastigotes results in disruption of the membrane stability, increase of membrane fluidity, failure to maintain lipid rafts, and hypersensitivity to heat stress along with altered morphology and cytokinesis defect. The effect deletion on lipid composition and sterol biosynthesis is a complete loss of ergostane-based sterols (5-dehydroepisterol, ergosterol, and episterol) and accumulation of toxic 14-methylated sterols
Leishmania infantum
physiological function
the enzyme is required for effective survival, normal proliferation and infectivity of Leishmania major parasites in the mammalian host. The enzyme is not required for promastigote survival or proliferation, but it is involved in the control of cell shape, differentiation, and division
Leishmania mexicana
physiological function
the enzyme is required for effective survival, normal proliferation and infectivity of Leishmania major parasites in the mammalian host. The enzyme is not required for promastigote survival or proliferation, but it is involved in the control of cell shape, differentiation, and division
Leishmania major
physiological function
the enzyme is required for effective survival, normal proliferation and infectivity of Leishmania major parasites in the mammalian host. The enzyme is not required for promastigote survival or proliferation, but it is involved in the control of cell shape, differentiation, and division
Leishmania infantum
General Information (protein specific)
General Information
Commentary
Organism
malfunction
inactivation of the enzyme in promastigotes results in disruption of the membrane stability, increase of membrane fluidity, failure to maintain lipid rafts, and hypersensitivity to heat stress along with altered morphology and cytokinesis defect. The effect deletion on lipid composition and sterol biosynthesis is a complete loss of ergostane-based sterols (5-dehydroepisterol, ergosterol, and episterol) and accumulation of toxic 14-methylated sterols
Leishmania mexicana
malfunction
inactivation of the enzyme in promastigotes results in disruption of the membrane stability, increase of membrane fluidity, failure to maintain lipid rafts, and hypersensitivity to heat stress along with altered morphology and cytokinesis defect. The effect deletion on lipid composition and sterol biosynthesis is a complete loss of ergostane-based sterols (5-dehydroepisterol, ergosterol, and episterol) and accumulation of toxic 14-methylated sterols
Leishmania major
malfunction
inactivation of the enzyme in promastigotes results in disruption of the membrane stability, increase of membrane fluidity, failure to maintain lipid rafts, and hypersensitivity to heat stress along with altered morphology and cytokinesis defect. The effect deletion on lipid composition and sterol biosynthesis is a complete loss of ergostane-based sterols (5-dehydroepisterol, ergosterol, and episterol) and accumulation of toxic 14-methylated sterols
Leishmania infantum
physiological function
the enzyme is required for effective survival, normal proliferation and infectivity of Leishmania major parasites in the mammalian host. The enzyme is not required for promastigote survival or proliferation, but it is involved in the control of cell shape, differentiation, and division
Leishmania mexicana
physiological function
the enzyme is required for effective survival, normal proliferation and infectivity of Leishmania major parasites in the mammalian host. The enzyme is not required for promastigote survival or proliferation, but it is involved in the control of cell shape, differentiation, and division
Leishmania major
physiological function
the enzyme is required for effective survival, normal proliferation and infectivity of Leishmania major parasites in the mammalian host. The enzyme is not required for promastigote survival or proliferation, but it is involved in the control of cell shape, differentiation, and division
Leishmania infantum
Other publictions for EC 1.14.13.70
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Synonyms
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
744274
Park
Nitric oxide stimulates cellu ...
Homo sapiens
Biochem. J.
474
3241-3252
2017
-
-
-
-
-
-
1
-
-
-
-
-
-
1
-
-
-
-
-
1
-
-
-
-
2
-
-
-
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1
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-
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-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
1
1
-
-
-
744843
Emami
An overview of azoles targeti ...
Leishmania major, Leishmania mexicana, Leishmania infantum
Eur. J. Med. Chem.
135
241-259
2017
-
6
-
-
-
-
39
-
-
-
-
-
-
3
-
-
-
-
-
6
-
-
6
-
-
-
-
-
-
-
-
-
-
-
-
4
-
6
-
-
-
-
-
4
39
-
-
-
-
-
-
-
-
-
-
-
6
-
-
6
-
-
-
-
-
-
-
-
-
-
6
6
-
-
-
744860
Borcea
-
Synthesis and molecular docki ...
Candida albicans SC5314
Farmacia
65
683-689
2017
-
-
-
-
-
-
10
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
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-
-
-
-
-
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-
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-
-
-
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-
-
10
-
-
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-
-
-
-
-
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-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
745117
Stana
Design, synthesis and antifun ...
Candida albicans SC5314
Int. J. Mol. Sci.
18
E177
2017
-
2
-
-
-
-
6
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
6
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
2
-
-
-
745378
Hargrove
Structural analyses of Candid ...
Candida albicans
J. Biol. Chem.
292
6728-6743
2017
-
-
1
1
-
-
8
1
-
-
-
-
-
1
-
-
1
-
-
-
-
-
1
-
1
-
-
-
1
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
8
-
1
-
-
-
-
-
-
-
1
-
-
-
-
1
-
-
-
-
1
-
-
-
-
-
-
-
-
1
1
745682
Alvarez-Rueda
The amino acid substitution N ...
Candida albicans
Med. Mycol.
54
764-775
2016
-
-
1
-
1
-
1
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
746216
Tyndall
Structural and functional elu ...
Saccharomyces cerevisiae, Saccharomyces cerevisiae YJM789
PLoS ONE
11
e0167485
2016
-
-
1
1
2
-
7
-
-
-
-
-
-
2
-
-
1
-
-
-
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
1
2
-
-
7
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
746454
Warrilow
Azole antifungal sensitivity ...
Malassezia globosa, Malassezia globosa CBS 7966
Sci. Rep.
6
27690
2016
-
-
1
-
-
-
4
3
-
-
-
-
-
2
-
-
1
-
-
-
-
-
5
-
1
1
-
-
3
1
-
-
-
-
-
4
-
-
1
-
-
-
-
4
4
-
3
-
-
-
-
-
-
-
1
-
-
-
-
5
-
1
-
-
3
1
-
-
-
-
-
-
-
3
3
744385
Morrison
Identification, modeling and ...
Danio rerio
Biochim. Biophys. Acta
1840
1825-1836
2014
-
-
1
-
-
-
2
-
-
-
-
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-
1
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-
-
-
-
1
-
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1
-
3
-
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-
1
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745522
Friggeri
Structural basis for rational ...
Trypanosoma cruzi, Trypanosoma cruzi CL Brener
J. Med. Chem.
57
6704-6717
2014
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