1.5.1.33: pteridine reductase
This is an abbreviated version!
For detailed information about pteridine reductase, go to the full flat file.
Word Map on EC 1.5.1.33
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1.5.1.33
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leishmania
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dihydrofolate
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trypanosoma
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antileishmanial
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antifolate
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promastigotes
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leishmaniasis
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trypanosomatids
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pterins
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donovani
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amastigotes
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trypanosomiasis
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dhfr-t
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trypanothione
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reductase-thymidylate
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tarentolae
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dihydrobiopterin
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glucantime
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medicine
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drug development
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pharmacology
- 1.5.1.33
- leishmania
- dihydrofolate
- trypanosoma
-
antileishmanial
- antifolate
- promastigotes
- leishmaniasis
-
trypanosomatids
- pterins
- donovani
- amastigotes
- trypanosomiasis
-
dhfr-t
- trypanothione
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reductase-thymidylate
- tarentolae
- dihydrobiopterin
-
glucantime
- medicine
- drug development
- pharmacology
Reaction
Synonyms
Atu1130, EC 1.1.1.253, H region methotrexate resistance protein, LaPTR1, LbPTR1, LdPTR1, LmPTR1, LpPTR1, More, NADPH-dependent short-chain dehydrogenase/reductase pteridine reductase, NADPH-dihydropteridine reductase, PruA, pteridine reductase, pteridine reductase 1, pteridine reductase I, PTR1, reductase, dihydropteridine (reduced nicotinamide adenine dinucleotide phosphate), Tb-PR, TbPTR1, tcptr1
ECTree
1.5.1.33 pteridine reductaseAdvanced search results
results (
results (Inhibitors
Inhibitors on EC 1.5.1.33 - pteridine reductase
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INHIBITOR 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
IMAGE
(1R,4S,6R)-4-hydroxy-3-methyl-6-(propan-2-yl)cyclohex-2-en-1-yl 5beta,8alpha,10alpha,13alpha-kaura-9(11),16-dien-18-oate
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(1R,4S,6R)-4-hydroxy-3-methyl-6-(propan-2-yl)cyclohex-2-en-1-yl 5beta,8alpha,9beta,10alpha,13alpha-kaur-16-en-18-oate
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(2E,4E,12E)-13-(benzo[d][1,3]dioxol-5-yl)-N-isobutyltrideca-2,4,12-trienamide
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(4-fluoro-phenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester
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(4-fluoro-phenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester
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treatment with 98 microM resulted in reduction of viable cells from 96.5% (control) to 9.86% after 5 h
(4S)-4-[[(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]phenyl)carbonyl]amino]-5-oxohexanoic acid
(Z)-5-(2-hydroxy-3-bromo-5-chlorobenzylidene)-thiazolidine-2,4-dione
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a noncompetitive inhibitor that binds in the same site as the cofactor
([5-[(1H-benzimidazol-2-yl)methyl]-1,3,4-oxadiazol-2-yl]sulfanyl)acetic acid
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([5-[(1H-benzimidazol-2-yl)methyl]-4H-1,2,4-triazol-3-yl]sulfanyl)acetic acid
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([5-[(6-nitro-1H-benzimidazol-2-yl)methyl]-1,3,4-oxadiazol-2-yl]sulfanyl)acetic acid
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([5-[(6-nitro-1H-benzimidazol-2-yl)methyl]-4H-1,2,4-triazol-3-yl]sulfanyl)acetic acid
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1-(3,4-dichlorophenyl)-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
competitive inhibition
1-(3,4-dichlorophenyl)-6-(4-nitrophenyl)-1,6-dihydro-1,3,5-triazine-2,4-diamine
competitive inhibition
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1-(4-chlorophenyl)-6-methyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
competitive inhibition
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1-(4-chlorophenyl)-6-propyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
competitive inhibition
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1-(4-methoxyphenyl)-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine
competitive inhibition
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1-[(4-[[6-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-4-carboxylic acid
1-[(4-[[8-amino-3-phenyl-6-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-4-carboxylic acid
2,4,6-triaminoquinazoline
i.e. TAQ, mimics the pterin head group of methotrexate, binds to the active site, binding structure and inhibition mechanism
2,4-diamino-6-[(E)-2-phenylethenyl]-7H-pyrrolo[2,3-d]-pyrimidine-5-carbonitrile
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2,4-diamino-6-[(Z)-2-(4-methylphenyl)ethenyl]-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
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2,4-diamino-6-[(Z)-2-phenylethenyl]-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
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2,4-diaminopyrimido[4,5-b]indol-6-ol
synthesis, inhibits TbPTR1 activity by competitive inhibition, binding mode, and structural characterization of its ternary complex with TbPTR1 and the cofactor NADP(H) from crystal structure, overview. The compound adopts a substrate-like orientation inside the cavity that maximizes the binding contributions of hydrophobic and hydrogen-bond interactions
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2,6-dimethyl [3-O-benzyl-1,2-O isopropylidene-beta-L-threo-pentofuronose-4-yl]-1-phenyl-1,4-dihydro pyridine-3,5-dicarboxylic acid diethyl ether
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2,6-dimethyl-4-(3-O-benzyl-1,2-O-isopropylidene-beta-L-threo pentofuranos-4-yl)-1-phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester
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oral therapy shows apoptosis like phenotypes targeting pteridine reductase 1 in intracellular amastigotes
2,6-dimethyl-4-(3-O-benzyl-1,2-ortho-isopropylidene-beta-L-threopentofuranos-4-yl)-1-phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester
treatment with 90 microM GDA resulted in reduction of viable cells from 94.2% (control) to 77.1%, 76.8%, 74.9%, 35.3% and 24.9% at 18, 24, 48, 72 and 96 h, respectively
2-amino-4-(thiomorpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
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2-amino-4-oxo-6-[(E)-2-phenylethenyl]-4,7-dihydro-3Hpyrrolo[2,3-d]pyrimidine-5-carbonitrile
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2-amino-4-[(propan-2-yl)oxy]-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
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2-amino-5,6-bis(4-chlorophenyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
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2-amino-5,6-bis(4-fluorophenyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
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2-amino-5,6-bis(4-methylphenyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
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2-amino-5-(3-chlorophenyl)-6-(4-fluorophenyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
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2-amino-5-(4-fluorophenyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
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2-amino-5-(4-methylphenyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
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2-amino-5-methyl-6-phenyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
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2-amino-6-(1,3-benzodioxol-5-yl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
2-amino-6-(3-formylphenyl)-4-(1-pyrrolidinyl)-7H-pyrrolo-[2,3-d]pyrimidine-5-carbonitrile
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2-amino-6-(4-bromophenyl)-5-phenyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
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2-amino-6-(4-fluorophenyl)-5-(4-methoxyphenyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
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2-amino-6-(4-fluorophenyl)-5-phenyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
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2-amino-6-bromo-4-(1-pyrrolidinyl)-7H-pyrrolo[2,3-d]-pyrimidine-5-carbonitrile
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2-amino-6-phenyl-5-(2-phenylethyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
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2-amino-6-[3-(methanesulfonyl)phenyl]-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
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2-amino-6-[4-(2-methylpropyl)phenyl]-5-phenyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
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2-amino-6-[4-(methanesulfonyl)phenyl]-5-phenyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
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2-amino-6-[4-[3-(4-morpholinyl)propyl]phenyl]-5-phenyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one trifluoroacetate
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4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-4H-pyrimidin-5-carboxylic acid ethyl ester
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both monastrol (R) and (S) enantiomers fit well in the ligand-binding pocket of LdPTR1. Monastrol is a potent inhibitor of PTR1 in Leishmania, it inhibits proliferation of amastigotes in macrophage cultures infected with an Leishmania donovani clinical isolate, with no host cytotoxicity
4-(4,6-diamino-2,2-dimethyl-1,3,5-triazin-1(2H)-yl)phenol
competitive inhibition
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5,6-bis(4-chlorophenyl)-N~4~,N~4~-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine
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5,6-bis(4-fluorophenyl)-N~4~,N~4~-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine
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5-(3-chlorophenyl)-6-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine
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5-(4-chlorophenyl)-1,3,5-triazaspiro[5.5]undeca-1,3-diene-2,4-diamine
competitive inhibition
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5-(4-fluorophenyl)-4-(2-methylpropoxy)-7H-pyrrolo[2,3-d]pyrimidin-2-amine
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5-(phenylethynyl)-4-(1-pyrrolidinyl)-7H-pyrrolo[2,3-d]-pyrimidin-2-amine
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5-[(6-chloro-1H-benzimidazol-2-yl)methyl]-1,3,4-oxadiazole-2-thiol
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5-[(6-chloro-1H-benzimidazol-2-yl)methyl]-4H-1,2,4-triazole-3-thiol
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5-[(6-nitro-1H-benzimidazol-2-yl)methyl]-1,3,4-oxadiazole-2-thiol
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5-[(6-nitro-1H-benzimidazol-2-yl)methyl]-4H-1,2,4-triazol-3-amine
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5-[(6-nitro-1H-benzimidazol-2-yl)methyl]-4H-1,2,4-triazole-3-thiol
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6-(4-fluorophenyl)-5-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine
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6-(4-fluorophenyl)-5-(4-methoxyphenyl)-N4,N4-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine
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6-(4-fluorophenyl)-N~4~,N~4~-dimethyl-5-phenyl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine
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6-[4-(2-methylpropyl)phenyl]-5-phenyl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine
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6-[4-(methanesulfonyl)phenyl]-5-phenyl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine
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cycloguanil
CYC, the known inhibitor of Plasmodial and Trypanosomal DHFR-TS enzymes is also as an inhibitor of TbPTR1
dimethyl 1-[(4-[[3-(ethoxycarbonyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-2,4-dicarboxylate
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dimethyl 1-[(4-[[3-phenyl-7-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-2,4-dicarboxylate
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ethyl 1-[(4-[[7-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-2-carboxylate
methyl 1-[(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]phenyl)carbonyl]piperidine-4-carboxylate
methyl 1-[(4-[[(2,4-diaminopteridin-6-yl)methyl]amino]phenyl)carbonyl]piperidine-4-carboxylate
N,N'-[tridecane-1,13-diylbis[(4,1-phenylene)methylene]]bis[1-(2-methoxyphenyl)methanamine]
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N-[3-(2,4-diamino-5-cyano-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl]methanesulfonamide
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N-[3-(2-amino-5-cyano-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl]methanesulfonamide
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N-[6-amino-5-(4-methoxyphenyl)-4,4-dimethyl-4,5-dihydrotriazin-2-yl]acetamide
competitive inhibition
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N4-cyclohexyl-5-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine
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(1R,4S,6R)-4-hydroxy-3-methyl-6-(propan-2-yl)cyclohex-2-en-1-yl 5beta,8alpha,10alpha,13alpha-kaura-9(11),16-dien-18-oate
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(1R,4S,6R)-4-hydroxy-3-methyl-6-(propan-2-yl)cyclohex-2-en-1-yl 5beta,8alpha,10alpha,13alpha-kaura-9(11),16-dien-18-oate
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(1R,4S,6R)-4-hydroxy-3-methyl-6-(propan-2-yl)cyclohex-2-en-1-yl 5beta,8alpha,10alpha,13alpha-kaura-9(11),16-dien-18-oate
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(1R,4S,6R)-4-hydroxy-3-methyl-6-(propan-2-yl)cyclohex-2-en-1-yl 5beta,8alpha,10alpha,13alpha-kaura-9(11),16-dien-18-oate
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(1R,4S,6R)-4-hydroxy-3-methyl-6-(propan-2-yl)cyclohex-2-en-1-yl 5beta,8alpha,9beta,10alpha,13alpha-kaur-16-en-18-oate
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(1R,4S,6R)-4-hydroxy-3-methyl-6-(propan-2-yl)cyclohex-2-en-1-yl 5beta,8alpha,9beta,10alpha,13alpha-kaur-16-en-18-oate
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(1R,4S,6R)-4-hydroxy-3-methyl-6-(propan-2-yl)cyclohex-2-en-1-yl 5beta,8alpha,9beta,10alpha,13alpha-kaur-16-en-18-oate
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(1R,4S,6R)-4-hydroxy-3-methyl-6-(propan-2-yl)cyclohex-2-en-1-yl 5beta,8alpha,9beta,10alpha,13alpha-kaur-16-en-18-oate
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(4S)-4-[[(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]phenyl)carbonyl]amino]-5-oxohexanoic acid
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(4S)-4-[[(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]phenyl)carbonyl]amino]-5-oxohexanoic acid
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1-[(4-[[6-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-4-carboxylic acid
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1-[(4-[[6-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-4-carboxylic acid
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1-[(4-[[8-amino-3-phenyl-6-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-4-carboxylic acid
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1-[(4-[[8-amino-3-phenyl-6-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-4-carboxylic acid
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2-(3,4-dihydroxyphenyl)-6-hydroxy-2,3-dihydro-4H-1-benzopyran-4-one
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2-(3,4-dihydroxyphenyl)-6-hydroxy-2,3-dihydro-4H-1-benzopyran-4-one
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2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
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2-amino-4-oxo-6-phenyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
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2-amino-4-oxo-6-phenyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
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2-amino-5-(2-phenylethyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
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2-amino-5-(2-phenylethyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
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2-amino-6-(1,3-benzodioxol-5-yl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
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2-amino-6-(1,3-benzodioxol-5-yl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
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2-amino-6-(3-formylphenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
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2-amino-6-(3-formylphenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
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2-amino-6-(4-ethylphenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
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2-amino-6-(4-ethylphenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
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2-amino-6-(4-methoxyphenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
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2-amino-6-(4-methoxyphenyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
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2-amino-6-bromo-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
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2-amino-6-bromo-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
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3alpha-cinnamoyloxy-9beta-hydroxy-ent-kaur-16-en-19-oic acid
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3alpha-cinnamoyloxy-9beta-hydroxy-ent-kaur-16-en-19-oic acid
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3alpha-cinnamoyloxy-9beta-hydroxy-ent-kaur-16-en-19-oic acid
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3alpha-p-coumaroyloxy-9beta-hydroxy-entkaur-16-en-19-oic acid
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3alpha-p-coumaroyloxy-9beta-hydroxy-entkaur-16-en-19-oic acid
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3alpha-p-coumaroyloxy-9beta-hydroxy-entkaur-16-en-19-oic acid
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6,6'-[1,4-phenylenebis(methyleneazanediyl)]bis(N-benzylhexanamide)
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6,6'-[1,4-phenylenebis(methyleneazanediyl)]bis(N-benzylhexanamide)
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6,6'-[methylenebis[(4,1-phenylene)methyleneazanediyl]]bis(N-benzylhexanamide)
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6,6'-[methylenebis[(4,1-phenylene)methyleneazanediyl]]bis(N-benzylhexanamide)
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6,6'-[[1,1'-biphenyl]-4,4'-diylbis(methyleneazanediyl)]bis(N-benzylhexanamide)
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6,6'-[[1,1'-biphenyl]-4,4'-diylbis(methyleneazanediyl)]bis(N-benzylhexanamide)
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6-hydroxy-2-(3-hydroxyphenyl)-2,3-dihydro-4H-1-benzopyran-4-one
the compound shows inhibitory activity both against the targeted enzyme and the parasite with a high selectivity and a low toxicity for humans. Only the (R)-isomer binds in the active site, 50% inhibition at 0.05 mM
6-hydroxy-2-(3-hydroxyphenyl)-2,3-dihydro-4H-1-benzopyran-4-one
the compound shows inhibitory activity both against the targeted enzyme and the parasite with a high selectivity and a low toxicity for humans. Only the (R)-isomer binds in the active site, 81% inhibition at 0.05 mM
6-[(3aR,9bS)-2,3,3a,9b-tetrahydro[1]benzopyrano[4,3-b]pyrrol-1(4H)-yl]hexan-1-amine
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6-[(3aR,9bS)-2,3,3a,9b-tetrahydro[1]benzopyrano[4,3-b]pyrrol-1(4H)-yl]hexan-1-amine
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ethyl 1-[(4-[[7-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-2-carboxylate
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ethyl 1-[(4-[[7-(trifluoromethyl)quinoxalin-2-yl]amino]phenyl)carbonyl]piperidine-2-carboxylate
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fischericin F
fischericin F is extracted from Ligularia fischeri. Fischericin F has ferulic acid as the main feature, bound to the ent-kaurane skeleton through an ester bond at C14
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fischericin F
fischericin F is extracted from Ligularia fischeri. Fischericin F has ferulic acid as the main feature, bound to the ent-kaurane skeleton through an ester bond at C14
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fischericin F
fischericin F is extracted from Ligularia fischeri. Fischericin F has ferulic acid as the main feature, bound to the ent-kaurane skeleton through an ester bond at C14
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fischericin F
fischericin F is extracted from Ligularia fischeri. Fischericin F has ferulic acid as the main feature, bound to the ent-kaurane skeleton through an ester bond at C14
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methyl 1-[(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]phenyl)carbonyl]piperidine-4-carboxylate
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methyl 1-[(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]phenyl)carbonyl]piperidine-4-carboxylate
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methyl 1-[(4-[[(2,4-diaminopteridin-6-yl)methyl]amino]phenyl)carbonyl]piperidine-4-carboxylate
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methyl 1-[(4-[[(2,4-diaminopteridin-6-yl)methyl]amino]phenyl)carbonyl]piperidine-4-carboxylate
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N,N'-[tridecane-1,13-diylbis[(4,1-phenylene)methylene]]bis[1-(2-methoxyphenyl)methanamine]
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N,N'-[tridecane-1,13-diylbis[(4,1-phenylene)methylene]]bis[1-(2-methoxyphenyl)methanamine]
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N1,N1-bis(4-fluorophenyl)-N2-(3-phenylpropyl)ethane-1,2-diamine
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N4-[([1,1'-biphenyl]-4-yl)methyl]pyrimidine-2,4,6-triamine
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additional information
an in-house database of 360 kauranes (tetracyclic diterpenes) is generated, and a combined ligand- and structure-based virtual screening (VS) approach is performed to select potential inhibitors of Leishmania major (Lm) pteridine reductase I (PTR1). The best-ranked kauranes are employed to verify the validity of the VS approach through LmPTR1 enzyme inhibition assay, molecular dynamics and docking calculations and simulations. Inhibitor synthesis and structure-activity relationship, enzyme-inhibitor interaction analysis using LmPTR1 crystal structure (PDB ID 1E7W) in complex with its respective inhibitor, methotrexate (PDB ID MTX), overview
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additional information
an in-house database of 360 kauranes (tetracyclic diterpenes) is generated, and a combined ligand- and structure-based virtual screening (VS) approach is performed to select potential inhibitors of Leishmania major (Lm) pteridine reductase I (PTR1). The best-ranked kauranes are employed to verify the validity of the VS approach through LmPTR1 enzyme inhibition assay, molecular dynamics and docking calculations and simulations. Inhibitor synthesis and structure-activity relationship, enzyme-inhibitor interaction analysis using LmPTR1 crystal structure (PDB ID 1E7W) in complex with its respective inhibitor, methotrexate (PDB ID MTX), overview
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additional information
a Cosseq genome-wide gain of function screen is performed against methotrexate and against the two thymidylate synthase inhibitors 5-fluorouracil and pemetrexed
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additional information
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a Cosseq genome-wide gain of function screen is performed against methotrexate and against the two thymidylate synthase inhibitors 5-fluorouracil and pemetrexed
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additional information
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the enzyme is considered a promising target for anti-leishmanial drug development and several inhibitors that share the substrate scaffold. Design of a series of thiazolidine-2,4-dione derivatives as PTR1 inhibitors by employing the thiazolidinone ring as a bioisosteric replacement for pteridine/purine ring, docking studies, molecular dynamics simulations, and inhibition mechanism, overview
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additional information
chromen-4-one derivatives as pteridine reductase 1 (PTR1) inhibitors, observed and predicted binding modes of the compounds, docking and modeling, overview. There are differences between the binding modes of the chromen-4-one and the chroman-4-one moiety. No inhibition by 3,6-dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one at 0.05 mM. Only the (R)-isomers bind in the active site
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additional information
docking study, structure-function analysis, and drug design. The effects of several factors on docking accuracy, including ligand and protein flexibility, are analyzed
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additional information
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docking study, structure-function analysis, and drug design. The effects of several factors on docking accuracy, including ligand and protein flexibility, are analyzed
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additional information
identification of a 2,4-diaminopyrimidine scaffold targeting Trypanosoma brucei pteridine reductase 1 from the LIBRA compound library screening campaign, screening of the LIBRA compound library against Trypanosoma brucei and Leishmania major pteridine reductase 1, TbPTR1 and LmPTR1, NMR study, overview. Nine compounds are active against parasitic PTR1 and are selected for cell-based parasite screening, as single agents and in combination with methotrexate (MTX). The most interesting TbPTR1 inhibitor identified is 4-(benzyloxy)pyrimidine-2,6-diamine (LIB_66). Subsequently, 6 different LIB_66 derivatives are synthesized to explore its structure-activity relationship (SAR) and absorption, distribution, metabolism, excretion and toxicity (ADMET) properties. The compounds are more inhibitory against the enzyme from Trypanosoma brucei compared to the enzyme from Leishmania major. Docking study and molecular modelling
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additional information
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identification of a 2,4-diaminopyrimidine scaffold targeting Trypanosoma brucei pteridine reductase 1 from the LIBRA compound library screening campaign, screening of the LIBRA compound library against Trypanosoma brucei and Leishmania major pteridine reductase 1, TbPTR1 and LmPTR1, NMR study, overview. Nine compounds are active against parasitic PTR1 and are selected for cell-based parasite screening, as single agents and in combination with methotrexate (MTX). The most interesting TbPTR1 inhibitor identified is 4-(benzyloxy)pyrimidine-2,6-diamine (LIB_66). Subsequently, 6 different LIB_66 derivatives are synthesized to explore its structure-activity relationship (SAR) and absorption, distribution, metabolism, excretion and toxicity (ADMET) properties. The compounds are more inhibitory against the enzyme from Trypanosoma brucei compared to the enzyme from Leishmania major. Docking study and molecular modelling
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additional information
design, docking, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction studies of 2-substituted-5-[(6-substituted-1H-benzimidazol-2yl)methyl]azole derivatives as PTR1 inhibitors. Molecular docking studies using the enzyme crystal structure (PDB ID 1E92) and detailed interaction analysis of compounds with the enzyme, overview. All compounds follow Lipinski's rule of five and can be considered as good oral candidates
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additional information
in silico identification and in vitro evaluation of natural inhibitors of Leishmania major pteridine reductase I. No inhibition by phillyrin, magnolin, and isosakuranetin. Docking study of inhibitors using the structure of LmPTR1 (PDB ID 2BFM), co-crystallized with NADP+, structure modeling, overview. Apart from salvianolic acid A (5), the most active inhibitors share structural features with certain similarities, such as engaging in Pi-Pi interactions with the nicotinamide moiety, namely, a flavone, a flavonol, a flavanone, or a four-chromanone system
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additional information
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in silico identification and in vitro evaluation of natural inhibitors of Leishmania major pteridine reductase I. No inhibition by phillyrin, magnolin, and isosakuranetin. Docking study of inhibitors using the structure of LmPTR1 (PDB ID 2BFM), co-crystallized with NADP+, structure modeling, overview. Apart from salvianolic acid A (5), the most active inhibitors share structural features with certain similarities, such as engaging in Pi-Pi interactions with the nicotinamide moiety, namely, a flavone, a flavonol, a flavanone, or a four-chromanone system
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additional information
an in-house database of 360 kauranes (tetracyclic diterpenes) is generated, and a combined ligand- and structure-based virtual screening (VS) approach is performed to select potential inhibitors of Leishmania major (Lm) pteridine reductase I (PTR1). The best-ranked kauranes are employed to verify the validity of the VS approach through LmPTR1 enzyme inhibition assay, molecular dynamics and docking calculations and simulations. Inhibitor synthesis and structure-activity relationship, enzyme-inhibitor interaction analysis using LmPTR1 crystal structure (PDB ID 1E7W) in complex with its respective inhibitor, methotrexate (PDB ID MTX), overview
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additional information
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an in-house database of 360 kauranes (tetracyclic diterpenes) is generated, and a combined ligand- and structure-based virtual screening (VS) approach is performed to select potential inhibitors of Leishmania major (Lm) pteridine reductase I (PTR1). The best-ranked kauranes are employed to verify the validity of the VS approach through LmPTR1 enzyme inhibition assay, molecular dynamics and docking calculations and simulations. Inhibitor synthesis and structure-activity relationship, enzyme-inhibitor interaction analysis using LmPTR1 crystal structure (PDB ID 1E7W) in complex with its respective inhibitor, methotrexate (PDB ID MTX), overview
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additional information
an in-house database of 360 kauranes (tetracyclic diterpenes) is generated, and a combined ligand- and structure-based virtual screening (VS) approach is performed to select potential inhibitors of Leishmania major (Lm) pteridine reductase I (PTR1). The best-ranked kauranes are employed to verify the validity of the VS approach through LmPTR1 enzyme inhibition assay, molecular dynamics and docking calculations and simulations. Inhibitor synthesis and structure-activity relationship, enzyme-inhibitor interaction analysis using LmPTR1 crystal structure (PDB ID 1E7W) in complex with its respective inhibitor, methotrexate (PDB ID MTX), overview
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additional information
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an in-house database of 360 kauranes (tetracyclic diterpenes) is generated, and a combined ligand- and structure-based virtual screening (VS) approach is performed to select potential inhibitors of Leishmania major (Lm) pteridine reductase I (PTR1). The best-ranked kauranes are employed to verify the validity of the VS approach through LmPTR1 enzyme inhibition assay, molecular dynamics and docking calculations and simulations. Inhibitor synthesis and structure-activity relationship, enzyme-inhibitor interaction analysis using LmPTR1 crystal structure (PDB ID 1E7W) in complex with its respective inhibitor, methotrexate (PDB ID MTX), overview
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additional information
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structure-based design and synthesis of 61 antiparasitic pyrrolopyrimidines targeting pteridine reductase 1, with input from crystal structures of 23 of these compounds complexed with enzyme PTR1, structure-activity relationships, inhibition mechanism, overview. Analysis of eight compounds sufficiently active in vivo evaluation in HEK cells, pharmacokinetic properties
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additional information
chromen-4-one derivatives as pteridine reductase 1 (PTR1) inhibitors, observed and predicted binding modes of the compounds, docking and modeling, overview. There are differences between the binding modes of the chromen-4-one and the chroman-4-one moiety. No inhibition by 3,6-dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one at 0.05 mM
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additional information
monocyclic and bicyclic aromatic systems have been proposed as inhibitors of Trypanosoma brucei PTR1 (TbPTR1), but the size of the catalytic cavity allows the accommodation of expanded molecular cores. Inhibitor development and evaluation, overview
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additional information
docking study, structure-function analysis, and drug design. The effects of several factors on docking accuracy, including ligand and protein flexibility, are analyzed
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additional information
identification of a 2,4-diaminopyrimidine scaffold targeting Trypanosoma brucei pteridine reductase 1 from the LIBRA compound library screening campaign, screening of the LIBRA compound library against Trypanosoma brucei and Leishmania major pteridine reductase 1, TbPTR1 and LmPTR1, NMR study, overview. Nine compounds are active against parasitic PTR1 and are selected for cell-based parasite screening, as single agents and in combination with methotrexate (MTX). The most interesting TbPTR1 inhibitor identified is 4-(benzyloxy)pyrimidine-2,6-diamine (LIB_66). Subsequently, 6 different LIB_66 derivatives are synthesized to explore its structure-activity-relationship (SAR) and absorption, distribution, metabolism, excretion and toxicity (ADMET) properties. The compounds are more inhibitory against the enzyme from Trypanosoma brucei compared to the enzyme from Leishmania major. Docking study and molecular modelling; N4,N6-dibenzylpyrimidine-2,4,6-triamine is not inhibitory
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additional information
successful dual inhibition of Trypanosoma brucei dihydrofolate reductase (TbDHFR, EC 1.5.1.3) and Trypanosoma brucei pteridine reductase 1 (TbPTR1) has implications in the exploitation of anti-folates. Molecular docking of a ligand library of 5742 compounds against TbPTR1 and identification of compounds showing promising binding modes. The protein-ligand complexes are subjected to molecular dynamics to characterize their molecular interactions and energetics, followed by in vitro testing. Five compounds show low micromolar Trypanosome growth inhibition in in vitro experiments that might be acting by inhibition of TbPTR1. Docking study with TbPTR1 and comparison with Trypanosoma cruzi PTR2, molecular dynamics, overview
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additional information
comparison of the X-ray crystal structure of the TbPTR1:NADP(H):CYC complex (PDB ID 6HNC) with the derivatives' structures 1-(3,4-dichlorophenyl)-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine (PDB ID 6HNR) and 1-(3,4-dichlorophenyl)-6-(4-nitrophenyl)-1,6-dihydro-1,3,5-triazine-2,4-diamine (PDB ID 6HOW). Selectivity of the ihibitors versus enzymes PTR1 and DHFR, overview
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additional information
successful dual inhibition of Trypanosoma brucei dihydrofolate reductase (TbDHFR, EC 1.5.1.3) and Trypanosoma brucei pteridine reductase 1 (TbPTR1) has implications in the exploitation of anti-folates. Molecular docking of a ligand library of 5742 compounds against TbPTR1 and identification of compounds showing promising binding modes. The protein-ligand complexes are subjected to molecular dynamics to characterize their molecular interactions and energetics, followed by in vitro testing. Five compounds show low micromolar Trypanosome growth inhibition in in vitro experiments that might be acting by inhibition of TbPTR1. Docking study with TbPTR1 and comparison with Trypanosoma cruzi PTR2, molecular dynamics, overview
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