1.1.1.267 (2-[[hydroxy(methyl)carbamoyl]oxy]ethyl)phosphonic acid - 258734 1.1.1.267 (2R)-3-[4-(hydroxymethyl)-4-[[4-(hydroxymethyl)phenyl]methyl]piperidin-1-yl]propane-1,2-diol - 258802 1.1.1.267 (2R)-3-[4-[2-[(cyclohexa-2,4-dien-1-yl)oxy]ethyl]-4-(hydroxymethyl)piperidin-1-yl]propane-1,2-diol - 258803 1.1.1.267 (2R)-3-[[[1-butyl-2-(cyclobutylmethanesulfonyl)-1H-imidazol-5-yl]methyl](methyl)amino]propane-1,2-diol - 258804 1.1.1.267 (2R,3R)-2,3,4-trihydroxybutyl dihydrogen phosphate IC50: 0.310 mM 60294 1.1.1.267 (2R,3R)-4-amino-2,3-dihydroxybutyl dihydrogen phosphate very weak inhibitor, IC50: 5 mM, above 60295 1.1.1.267 (2R,3S)-2,3-dihydroxy-4-(hydroxyamino)-4-oxobutyl dihydrogen phosphate very weak inhibitor, IC50: 5 mM, above 60292 1.1.1.267 (2R,3S)-4-amino-2,3-dihydroxy-4-oxobutyl dihydrogen phosphate IC50: 0.253 mM 60293 1.1.1.267 (2S,3R)-2,3-dihydroxy-4-phosphonooxybutyric acid IC50: 0.551 mM 62246 1.1.1.267 (2S,3R)-dihydroxybutyramide 4-phosphate 50% inhibition at 0.09 mM 122912 1.1.1.267 (2S,3R)-methyl 2,3-dihydroxy-4-phosphonooxybutyrate IC50: 1.024 mM 62247 1.1.1.267 (3-(hydroxy[(pentafluorophenyl)carbonyl]amino)propyl)phosphonic acid - 67751 1.1.1.267 (3-(N-hydroxyacetamido)-1-phenyl)propylphosphonic acid 92% inhibition at 0.1 mM 89584 1.1.1.267 (3-acetamidopropyl)phosphonic acid - 258818 1.1.1.267 (3-boronopropyl)phosphonic acid MIC90 = 0.053 mg/ml 258819 1.1.1.267 (3-[hydroxy(5-oxohexanoyl)amino]propyl)phosphonic acid - 67752 1.1.1.267 (3-[hydroxy(6-phenylhexanoyl)amino]propyl)phosphonic acid - 67753 1.1.1.267 (3-[hydroxy(hexadecanoyl)amino]propyl)phosphonic acid - 67754 1.1.1.267 (3R)-1-(2,2-dimethylpropyl)-3-hydroxy-3-([[(5-methyl-4H-1,2,4-triazol-3-yl)methyl]amino]methyl)piperidin-2-one - 258821 1.1.1.267 (3S)-1-(cyclopropylmethyl)-3-([[(4,5-dimethyl-1,3-thiazol-2-yl)methyl]amino]methyl)-3-hydroxypiperidin-2-one - 258824 1.1.1.267 (3S)-hydroxypentan-2-one 5-phosphate 50% inhibition at 0.03 mM 122914 1.1.1.267 (3S,4R)-3,4-dihydroxy-4-methyl-5-oxohexylphosphonic acid - 74702 1.1.1.267 (3S,4R)-3-((2S)-1-(6,7-dimethoxy-4-(pyrrolidin-1-yl)-1,7,8,8a-tetrahydroquinazolin-2-yl)-4-hydroxybutan-2-yl)-4-hydroxytetrahydrothiophene 1,1-dioxide - 258828 1.1.1.267 (4-chloro-2-[[1-(2,3-dihydroxypropyl)piperidin-4-yl]oxy]phenyl)(piperidin-1-yl)methanone - 258830 1.1.1.267 (4-hydrazinyl-4-oxobutyl)phosphonic acid - 258832 1.1.1.267 (4-[[3-(hydroxymethyl)phenyl]amino]-4-oxobutyl)phosphonic acid 26.8% inhibition 89591 1.1.1.267 (4-[[3-(hydroxymethyl)phenyl]amino]-4-oxobutyl)phosphonic acid - 89591 1.1.1.267 (4S)-hydroxypentan-2-one 5-phosphate 50% inhibition at 0.15 mM 122913 1.1.1.267 (5R)-5-[1-[(2R)-2,3-dihydroxypropyl]piperidin-4-yl]-5-(3-phenylpropyl)imidazolidine-2,4-dione - 258858 1.1.1.267 (pyridin-2-ylmethyl)phosphonic acid - 89592 1.1.1.267 ([[acetyl(hydroxy)amino]methoxy]methyl)phosphonic acid - 259015 1.1.1.267 ([[formyl(hydroxy)amino]methoxy]methyl)phosphonic acid - 259016 1.1.1.267 1,1,1-trifluoro-1-deoxy-D-xylulose 5-phosphoric acid i.e. CF3-DXP, very low inhibition 62243 1.1.1.267 1,1-difluoro-1-deoxy-D-xylulose 5-phosphoric acid i.e. CF2-DXP, very low inhibition 62244 1.1.1.267 1,2-dideoxy-D-hexulose 6-phosphate i.e. Et-DXP, very low inhibition 62245 1.1.1.267 1,2-dideoxy-D-threo-3-hexulose 6-phosphate 50% inhibition at 0.63 mM 13661 1.1.1.267 1,2-dideoxy-D-threo-3-hexulose 6-phosphate weak, competitive inhibition, a highly conserved tryptophan residue in the flexible loop is blocked by the substrate analog 13661 1.1.1.267 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole i.e. PPT, lead molecule as inhibitor of IspC 259764 1.1.1.267 1-deoxy-D-xylulose 5-phosphate substrate inhibition 1263 1.1.1.267 1-deoxy-L-ribulose 5-phosphate 50% inhibition at 0.18 mM 122911 1.1.1.267 1-hydroxy-5-phenylpyridin-2(1H)-one minimal inhibitory concentration for growth 0.02 mM 12129 1.1.1.267 1-hydroxy-5-phenylpyridin-2(1H)-one minimal inhibitory concentration for growth 0.1 mM 12129 1.1.1.267 1-hydroxy-5-phenylpyridin-2(1H)-one minimal inhibitory concentration for growth 0.05 mM 12129 1.1.1.267 1-hydroxy-5-phenylpyridin-2(1H)-one - 12129 1.1.1.267 1-[(2S)-2,3-dihydroxypropyl]-N-[3-(furan-2-yl)phenyl]piperidine-4-carboxamide - 259093 1.1.1.267 13-methyl-[1,3]benzodioxolo[5,6-c]-1,3-dioxolo[4,5-i]phenanthridinium chloride i.e. sanguinarine chloride, lead molecule as inhibitor of IspC 259766 1.1.1.267 2-[(5Z)-5-(3,4-dihydroxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-N-hydroxyacetamide inhibitor keeps its inhibition capacity in the presence of Triton X-100 and shows antimicrobial activity against Escherichia coli 215565 1.1.1.267 2-[acetyl(hydroxy)amino]ethyl phosphate - 259217 1.1.1.267 2-[acetyl(methyl)amino]ethyl phosphate - 259218 1.1.1.267 2-[formyl(hydroxy)amino]ethyl phosphate - 259219 1.1.1.267 3'-[(8-cinnamoyl-5,7-dihydroxy-2,2-dimethyl-2H-1-benzopyran-6-yl)methyl]-2',4',6'-trihydroxy-5'-methylacetophenone i.e. rottlerin, lead molecule as inhibitor of IspC 259765 1.1.1.267 3,3-dimethyl-11-phenyl-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one the inhibitor is believed to hamper the captivating step of the synthetic pathway, as a result of which inadequacy of IPP pool will definitely foster the endurance of parasite in the intraerythrocytic stage 259224 1.1.1.267 3-(3,5-dibromo-4-hydroxybenzylidine-5-iodo-1,3-dihydro-indol-2-one) i.e. GW5074, lead molecule as inhibitor of IspC 259763 1.1.1.267 3-(hydroxy([(2-phenylbutanoyl)amino]acetyl)amino)propylphosphonic acid - 26573 1.1.1.267 3-(hydroxy([(3-methylbutanoyl)amino]acetyl)amino)propylphosphonic acid - 26572 1.1.1.267 3-(hydroxy([(4-phenoxybutanoyl)amino]acetyl)amino)propylphosphonic acid - 26578 1.1.1.267 3-(hydroxy([(4-phenylbutanoyl)amino]acetyl)amino)propylphosphonic acid - 26574 1.1.1.267 3-(hydroxyamino)-3-oxopropyl phosphate - 259257 1.1.1.267 3-(N-hydroxyacetamido)-1-(3,4-dichlorophenyl)propylphosphonic acid - 89577 1.1.1.267 3-(N-hydroxyformamido)-1-(2-bromophenyl)propylphosphonic acid 93% inhibition at 0.1 mM 89579 1.1.1.267 3-(N-hydroxyformamido)-1-(3,4-dichlorophenyl)propylphosphonic acid - 89575 1.1.1.267 3-([(1H-indol-3-yl)acetyl]amino)propylphosphonic acid - 74705 1.1.1.267 3-([2-(methoxycarbonyl)benzoyl]amino)propylphosphonic acid - 74706 1.1.1.267 3-([3-(1H-indol-3-yl)propanoyl]amino)propylphosphonic acid - 74704 1.1.1.267 3-([4-(1H-indol-3-yl)butanoyl]amino)propylphosphonic acid - 74703 1.1.1.267 3-fluoro-1-deoxy-D-xylulose-5-phosphate noncompetitive 55877 1.1.1.267 3-[(([(3,4-dimethoxyphenyl)acetyl]amino)acetyl)(hydroxy)amino]propylphosphonic acid - 26576 1.1.1.267 3-[(2-hydroxybenzoyl)amino]propylphosphonic acid - 74707 1.1.1.267 3-[(3,4-diethoxybenzoyl)amino]propylphosphonic acid - 74708 1.1.1.267 3-[(3,4-dimethoxybenzoyl)amino]propylphosphonic acid - 74711 1.1.1.267 3-[(4-methylpentanoyl)amino]propylphosphonic acid - 74709 1.1.1.267 3-[(4-phenoxybenzoyl)amino]propylphosphonic acid - 74710 1.1.1.267 3-[([(cyclopropylcarbonyl)amino]acetyl)(hydroxy)amino]propylphosphonic acid - 26575 1.1.1.267 3-[hydroxy(([3-(trifluoromethoxy)benzoyl]amino)acetyl)amino]propylphosphonic acid - 26577 1.1.1.267 3-[hydroxy(([4-(1H-indol-3-yl)butanoyl]amino)acetyl)amino]propylphosphonic acid - 26571 1.1.1.267 3-[hydroxy(methyl)amino]-3-oxopropyl phosphate - 259300 1.1.1.267 4-(1-(4-hydroxy-2-oxo-2H-chromen-3-yl)-2-methylpropyl)-5-methyl-2-(4-nitrophenyl)-1,2-dihydro-3H-pyrazol-3-one - 259305 1.1.1.267 4-(N-formyl-N-hydroxy-amino)-butyric acid - 62239 1.1.1.267 4-benzylbenzene-1,2-diol minimal inhibitory concentration for growth 0.2 mM 19317 1.1.1.267 4-benzylbenzene-1,2-diol minimal inhibitory concentration for growth 1 mM 19317 1.1.1.267 4-benzylbenzene-1,2-diol - 19317 1.1.1.267 4-butyl-6-[4-([[(2R)-2,3-dihydroxypropyl](methyl)amino]methyl)phenyl]pyridin-2(1H)-one - 259324 1.1.1.267 4-fluoro-1-deoxy-D-xylulose-5-phosphate noncompetitive 55878 1.1.1.267 5-[hydroxy(methyl)amino]-5-oxopentanoic acid - 259437 1.1.1.267 Arbutus andrachne plant extract - 143599 1.1.1.267 baicalein - 1102 1.1.1.267 biphenyl-3,4-diol minimal inhibitory concentration for growth 0.2 mM 14960 1.1.1.267 biphenyl-3,4-diol minimal inhibitory concentration for growth 0.5 mM 14960 1.1.1.267 carvacrol 55.6% inhibition of DXR 6150 1.1.1.267 carveol 23.2% inhibition of DXR 170667 1.1.1.267 catechin - 1437 1.1.1.267 catechin 3.35% inhibition 1437 1.1.1.267 Cercis siliquastrum leaf extract high inhibitory activity 143594 1.1.1.267 Chloroquine - 1439 1.1.1.267 Cu2+ - 19 1.1.1.267 diethyl (1-(3,4-dichlorophenyl)-3-(N-hydroxyacetamido)propyl)phosphonate - 89574 1.1.1.267 diethyl (1-(3,4-dichlorophenyl)-3-(N-hydroxyformamido)propyl)phosphonate - 89573 1.1.1.267 diethyl (2-[[(furan-2-yl)methyl]amino]-2-oxoethyl)phosphonate - 259515 1.1.1.267 diethyl (2-[[3-(hydroxymethyl)phenyl]amino]-2-oxoethyl)phosphonate 40.4% inhibition 89587 1.1.1.267 diethyl (2-[[3-(hydroxymethyl)phenyl]amino]-2-oxoethyl)phosphonate - 89587 1.1.1.267 diethyl (3-[[3-(hydroxymethyl)phenyl]amino]-3-oxopropyl)phosphonate 17.9% inhibition 174559 1.1.1.267 diethyl [2-(3-hydroxyanilino)-2-oxoethyl]phosphonate 43.9% inhibition at 0.25 mM 223700 1.1.1.267 diethyl [2-(3-hydroxyanilino)-2-oxoethyl]phosphonate 45.2% inhibition at 0.25 mM 223700 1.1.1.267 diethyl [2-oxo-2-[(1,3-thiazol-2-yl)amino]ethyl]phosphonate - 259516 1.1.1.267 diethyl [2-oxo-2-[(pyridin-2-yl)amino]ethyl]phosphonate - 259517 1.1.1.267 diethyl [2-[(3-bromophenyl)amino]-2-oxoethyl]phosphonate 21.4% inhibition 174563 1.1.1.267 diethyl [2-[(3-cyanophenyl)amino]-2-oxoethyl]phosphonate 11.9% inhibition 89586 1.1.1.267 diethyl [2-[(3-cyanophenyl)amino]-2-oxoethyl]phosphonate - 89586 1.1.1.267 diethyl [2-[(3-hydroxyphenyl)amino]-2-oxoethyl]phosphonate 24.4% inhibition 89585 1.1.1.267 diethyl [2-[(3-hydroxyphenyl)amino]-2-oxoethyl]phosphonate - 89585 1.1.1.267 diethyl [2-[(3-methoxyphenyl)amino]-2-oxoethyl]phosphonate 11% inhibition 174561 1.1.1.267 diethyl [2-[3-(hydroxymethyl)anilino]-2-oxoethyl]phosphonate 40.4% inhibition at 0.25 mM 259518 1.1.1.267 diethyl [2-[3-(hydroxymethyl)anilino]-2-oxoethyl]phosphonate 40.7% inhibition at 0.25 mM 259518 1.1.1.267 diethyl [3-(3-hydroxyanilino)-3-oxopropyl]phosphonate 49.2% inhibition at 0.25 mM 259519 1.1.1.267 diethyl [3-[(3-hydroxyphenyl)amino]-3-oxopropyl]phosphonate 33.5% inhibition 174560 1.1.1.267 diethyl [3-[(3-methoxyphenyl)amino]-3-oxopropyl]phosphonate 14.1% inhibition 174562 1.1.1.267 diethyl [3-[3-(hydroxymethyl)anilino]-3-oxopropyl]phosphonate 17.9% inhibition at 0.25 mM 259520 1.1.1.267 EDTA - 21 1.1.1.267 EDTA complete inhibition at 5 mM 21 1.1.1.267 epigallocatechin gallate specifically inhibits the enzyme and has antimicrobial activity, competitive inhibition versus DXP and uncompetitive inhibition versus NADPH 1234 1.1.1.267 ethyl 1-[(2R)-2,3-dihydroxypropyl]-4-(2-phenoxyethyl)piperidine-4-carboxylate - 259531 1.1.1.267 ethyl 1-[(2R)-2,3-dihydroxypropyl]-4-[[2-(trifluoromethyl)phenyl]methyl]piperidine-4-carboxylate - 259532 1.1.1.267 ethyl 2-(2-ethoxy-2-oxoethyl)-2,5-dihydro-1H-benzo[b][1,4]diazepine-3-carboxylate the inhibitor is believed to hamper the captivating step of the synthetic pathway, as a result of which inadequacy of IPP pool will definitely foster the endurance of parasite in the intraerythrocytic stage 259533 1.1.1.267 ethyl hydrogen [1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonate - 89576 1.1.1.267 ethyl hydrogen [3-[acetyl(hydroxy)amino]-1-(3,4-dichlorophenyl)propyl]phosphonate - 89578 1.1.1.267 ethyl hydrogen [3-[acetyl(hydroxy)amino]-1-[2-(pyridin-3-yl)phenyl]propyl]phosphonate 20% inhibition at 0.1 mM 174553 1.1.1.267 eugenol 68.3% inhibition of DXR 909 1.1.1.267 Fe2+ - 25 1.1.1.267 fosfoxacin phosphate analogue of fosmidomycin 62237 1.1.1.267 fosfoxacin - 62237 1.1.1.267 fosmidomycin - 1364 1.1.1.267 fosmidomycin 50% inhibition at 0.0035 mM 1364 1.1.1.267 fosmidomycin model for tight-binding mode of inhibition 1364 1.1.1.267 fosmidomycin acts by binding strongly to DXR as a slow tight-binding inhibitor, inhibitor-enzyme interaction and structure analysis for design of inhibitors, possibly mimics a transition state in the reaction coordinate of the substrate, the initial rapid equilibrium is subject to negative cooperativity, overview 1364 1.1.1.267 fosmidomycin IC50: 310 nM for the forward reaction, 0.0027 mM for the reverse reaction, Gram positive bacteria, including Mycobacterium tuberculosis, are resistant against the antibiotic fosmidomycin, which is an inhibitor of the enzyme from most gram-negative bacteria and other organisms 1364 1.1.1.267 fosmidomycin a natural antibiotic from Streptomyces lavendulae, a specific, mixed type inhibitor, the N-formyl-N-hydroxy amino headgroup of fosmidomycin coordinates Mg2+ ion forming an octahedral complex with active site residues Asp157, Glu159, and Glu241 and a critical binding site water molecule, residue His219 is essential for placing fosmidomycin in the active site for optimal catalysis, mechanism, overview, NADPH has a vital role in tight binding of the inhibitor within the enzyme active site 1364 1.1.1.267 fosmidomycin a phosphonic metabolite from Streptomyces rubellomurinus 1364 1.1.1.267 fosmidomycin IC50: 450 nM, recombinant enzyme, inhibition of growth and forskolin production in vivo 1364 1.1.1.267 fosmidomycin analysis of parasite growth in infected cultured erythrocytes. 50% growth inhibition at about 301 nM 1364 1.1.1.267 fosmidomycin potent inhibitor but with very short half-life in plasma and low oral availability 1364 1.1.1.267 fosmidomycin a natural product isolated from Streptomyces lavendulae 1364 1.1.1.267 fosmidomycin a naturally occurring retrohydroxamate phosphonic acid. DXR-NADPH-fosmidomycin complex crystal structure analysis, the phosphonate group of the inhibitor is located in the phosphate binding cleft of the substrate DXP and is bound in a similar fashion as the phosphate group 1364 1.1.1.267 fosmidomycin a natural product, which forms a chelate with the active site divalent metal ion (Mg2+/Mn2+) through its hydroxamate metal-binding group. Competitive versus 1-deoxy-D-xylulose 5-phosphate, uncompetitive versus NADPH, strong inhibition 1364 1.1.1.267 fosmidomycin a natural product, which forms a chelate with the active site divalent metal ion (Mg2+/Mn2+) through its hydroxamate metal-binding group. Competitive versus 1-deoxy-D-xylulose 5-phosphate, uncompetitive versus NADPH 1364 1.1.1.267 fosmidomycin a natural product, which forms a chelate with the active site divalent metal ion (Mg2+/Mn2+) through its hydroxamate metal-binding group. Competitive versus 1-deoxy-D-xylulose 5-phosphate, uncompetitive versus NADPH. No or poor inhibition by diethyl [3-[3-(hydroxymethyl)anilino]-3-oxopropyl]phosphonate, diethyl [3-(3-hydroxyanilino)-3-oxopropyl]phosphonate, and [3-(3-methoxyanilino)-3-oxopropyl]phosphonic acid 1364 1.1.1.267 fosmidomycin the DXR inhibitor shows safety as well as efficacy against Plasmodium falciparum malaria in clinical trials 1364 1.1.1.267 fosmidomycin analogues synthesis, stereochemistry, and analysis of inhibitory potency of several fosmidomycin analogues, overview 135280 1.1.1.267 FR 900098 N-acetyl analogue of fosmidomycin 135279 1.1.1.267 FR-900098 - 16671 1.1.1.267 FR-900098 fosmidomycin homologue 16671 1.1.1.267 FR-900098 a naturally occurring retrohydroxamate phosphonic acid, isolated from the filtrate of a Pseudomonas fluorescens PK-52 culture 16671 1.1.1.267 FR900098 N-acetyl analogue of fosmidomycin 4712 1.1.1.267 FR900098 - 4712 1.1.1.267 FR900098 specific inhibition 4712 1.1.1.267 FR900098 analysis of parasite growth in infected cultured erythrocytes. 50% growth inhibition at about 118 nM 4712 1.1.1.267 FR900098 N-acetyl homologue of fosmidomycin 4712 1.1.1.267 FR900098 fosmidomycin homologue 4712 1.1.1.267 FR900098 an acetyl analogue of fosmidomycin 4712 1.1.1.267 FR900098 a naturally occurring retrohydroxamate phosphonic acid 4712 1.1.1.267 gallocatechin gallate completely suppresses the activity of DXR at 100 microM, and shows around 50% DXR inhibition at 25 microM 6836 1.1.1.267 gallocatechin gallate specifically inhibits the enzyme and has antimicrobial activity, competitive inhibition versus DXP and uncompetitive inhibition versus NADPH 6836 1.1.1.267 gallocatechin gallate strong inhibition of DXR, isolated from Camellia sinenesis 6836 1.1.1.267 Geranium molle plant extract - 143597 1.1.1.267 Helianthemum ventosum plant extract - 143595 1.1.1.267 Helianthemum vesicarium plant extract - 143596 1.1.1.267 linalool 22.7% inhibition of DXR 2852 1.1.1.267 methyl jasmonate - 2525 1.1.1.267 methyl N-([(3S)-1-[(2,3-difluorophenyl)methyl]-3-hydroxy-2-oxopiperidin-3-yl]methyl)glycinate - 259554 1.1.1.267 additional information 1,1,1-trifluoro-1-deoxy-D-xylulose 5-phosphoric acid, 1,1-difluoro-1-deoxy-D-xylulose 5-phosphoric acid, and 1,2-dideoxy-D-hexulose 6-phosphate are poor inhibitors, most likely because of the increase in steric bulk at C1 2 1.1.1.267 additional information no substrate inhibition by 2-C-methyl-D-erythritol 4-phosphate, NADPH or NADP+ 2 1.1.1.267 additional information design and development of inhibitors, structure and docking modeling, overview 2 1.1.1.267 additional information inhibitor design and synthesis, overview 2 1.1.1.267 additional information neither the sulfone (N-hydroxy-N-[3-(alkylsulfonyl)propyl]acetamides) nor the sulfonamide derivatives (N-hydroxy-N-(3-sulfamoylpropyl) acetamide and N-hydroxy-N-(3-(N-alkylsulfamoyl)propyl)acetamide) of FR900098 display any significant inhibitory activity against DXR at a concentration of 0.03 mM. Importance of the negative charge for the binding of fosmidomycin-like inhibitors to DXR. Uncharged molecules are virtually inactive whereas derivatives that possess only one instead of two negative charges are markedly less active. It is possible to regain some of the activity that is lost by the reduction of the charge by occupation of hitherto unexploited areas of the enzyme 2 1.1.1.267 additional information pyridine-containing fosmidomycin derivative inhibitor design and development using quantitative structure?activity relationship and crystallographic studies, synthesis, overview 2 1.1.1.267 additional information inhibitor design and synthesis, structure-activity relationship profile for the inhibition of TgDXR, overview 2 1.1.1.267 additional information inhibitory potencies of a series of aryl- and heteroarylcarbamoylphosphonic acids, their diethyl esters and disodium salts as analogues of the potent DXR inhibitor fosmidomycin, effects of the carboxamide N-substituents and the length of the methylene linker, in silico docking studies, saturation transfer difference NMR spectroscopy and enzyme inhibition assays, overview. Molecular modelling and simulated docking studies. No or poor inhibition by diethyl (4-[[3-(hydroxymethyl)phenyl]amino]-4-oxobutyl)phosphonate, diethyl [5-[(3-hydroxyphenyl)amino]-5-oxopentyl]phosphonate, [3-[(3-hydroxyphenyl)amino]-3-oxopropyl]phosphonic acid, [5-[(3-bromophenyl)amino]-5-oxopentyl]phosphonic acid, diethyl [5-[(3-methoxyphenyl)amino]-5-oxopentyl]phosphonate, [4-[(3-methoxyphenyl)amino]-4-oxobutyl]phosphonic acid, [5-[(3-methoxyphenyl)amino]-5-oxopentyl]phosphonic acid, diethyl [4-[(3-bromophenyl)amino]-4-oxobutyl]phosphonate, [4-[(3-bromophenyl)amino]-4-oxobutyl]phosphonic acid, and [5-[(3-bromophenyl)amino]-5-oxopentyl]phosphonic acid 2 1.1.1.267 additional information inhibitory potencies of a series of aryl- and heteroarylcarbamoylphosphonic acids, their diethyl esters and disodium salts as analogues of the potent DXR inhibitor fosmidomycin, effects of the carboxamide N-substituents and the length of the methylene linker, in silico docking studies, saturation transfer difference NMR spectroscopy and enzyme inhibition assays, overview. Molecular modelling and simulated docking studies. No or poor inhibition by diethyl [3-[(3-hydroxyphenyl)amino]-3-oxopropyl]phosphonate, diethyl [2-[(3-methoxyphenyl)amino]-2-oxoethyl]phosphonate, diethyl [3-[(3-methoxyphenyl)amino]-3-oxopropyl]phosphonate, diethyl [2-[(3-bromophenyl)amino]-2-oxoethyl]phosphonate, diethyl (3-[[3-(hydroxymethyl)phenyl]amino]-3-oxopropyl)phosphonate, [4-[(3-methoxyphenyl)amino]-4-oxobutyl]phosphonic acid, and [2-[(3-cyanophenyl)amino]-2-oxoethyl]phosphonic acid 2 1.1.1.267 additional information development and evaluation of a high-throughput screening spectrometric assay, measuring Dxr activity of Dxr coupled with 1-deoxy-D-xylulose-5-phosphate synthase, Dxs, activity, for simultaneous selection of inhibitors of the enzyme, overview 2 1.1.1.267 additional information design, synthesis, and X-ray crystallographic studies of alpha-aryl 3,4-dichlorophenyl-substituted fosmidomycin analogues as enzyme inhibitors. The introduction of a 3,4-dichlorophenyl group in the Calpha-position relative to the phosphonate group produces analogues that have a higher in vitro antimalarial activity than fosmidomycin 2 1.1.1.267 additional information use of the Dxr-fosmidomycin cocrystal structure to design bisubstrate ligands to bind to both the 1-deoxy-D-xylulose-5-phosphate and NADPH sites 2 1.1.1.267 additional information the methyl erythritol phosphate (MEP) pathway represents an attractive series of targets for antibiotic design, considering each enzyme of the pathway is both essential and has no human homologues. MEP pathway inhibitors (collectively called MEPicides) are most often rationally designed on the fosmidomycin scaffold, balancing target specificity with bioavailability. Pilot scale high-throughput screening (HTS) campaign against the first and second committed steps in the pathway, catalyzed by DXP reductoisomerase (IspC) and MEP cytidylyltransferase (IspD), using compounds present in the commercially available LOPAC1280 library as well as in an in-house natural product extract library. Analysis of mechanism of inhibition, most compounds function through aggregation. The method is useful for quickly screening a chemical library, while effectively identifying false positive compounds associated with assay constraints and aggregation. Screening using Yersinia pestis subsp. A1122, Mycobacterium tuberculosis, and Francisella tularensis subsp. novicida strain Utah 112, overview. Inhibition is attenuated in the presence of Triton X-100 for all inhibitors except sanguinarine chloride and suramin hexasodium 2 1.1.1.267 additional information the methyl erythritol phosphate (MEP) pathway represents an attractive series of targets for antibiotic design, considering each enzyme of the pathway is both essential and has no human homologues. MEP pathway inhibitors (collectively called MEPicides) are most often rationally designed on the fosmidomycin scaffold, balancing target specificity with bioavailability. Pilot scale high-throughput screening (HTS) campaign against the first and second committed steps in the pathway, catalyzed by DXP reductoisomerase (IspC) and MEP cytidylyltransferase (IspD), using compounds present in the commercially available LOPAC1280 library as well as in an in-house natural product extract library. Analysis of mechanism of inhibition, most compounds function through aggregation. The method is useful for quickly screening a chemical library, while effectively identifying false positive compounds associated with assay constraints and aggregation. Screening using Yersinia pestis strain A1122, Mycobacterium tuberculosis, and Francisella tularensis subsp. novicida strain Utah 112, overview. Inhibition is attenuated in the presence of Triton X-100 for all inhibitors except sanguinarine chloride and suramin hexasodium 2 1.1.1.267 additional information possible interactions between DXR and the catechine inhibitors are simulated via molecular docking simulation, detailed overview. Triton X-100 does not affect the inhibition of the enzyme by epigallocatechin gallate and gallocatechin gallate, but that by baicalein (positive control) 2 1.1.1.267 additional information hydroxamate analogues of fosfoxacin, the phosphate homologue of fosmidomycin, as inhibitors of DXR, synthesis and activities, analysis of Escherichia coli strain XL-1 Blue cell growth inhibition, overview 2 1.1.1.267 additional information hydroxamate analogues of fosfoxacin, the phosphate homologue of fosmidomycin, as inhibitors of DXR, synthesis and activities, overview 2 1.1.1.267 additional information non-hydroxamate inhibitors of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), docking study, structure-activity analysis, overview. No inhibiton at 0.02 mM by [3-(3-methoxyanilino)-3-oxopropyl]phosphonic acid or [3-[benzyl(pyridin-2-yl)amino]-3-oxopropyl]phosphonic acid or [3-[benzyl(3-hydroxyphenyl)amino]-3-oxopropyl]phosphonic acid or [2-[(sulfanylcarbonothioyl)amino]ethyl]phosphonic acid or [3-[(sulfanylcarbonothioyl)amino]propyl]phosphonic acid or [3-(2,3-dihydroxyphenyl)propyl]phosphonic acid 2 1.1.1.267 additional information non-hydroxamate inhibitors of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), docking study, structure-activity analysis, overview 2 1.1.1.267 additional information in silico identification and biological evaluation of inhibitors targeting 1-deoxy-D-xylulose-5-phosphate reductoisomerase, structure-based computational approach and biological evaluation, docking and binding mode estimation and molecular dynamics simulation, overview. Inhibitor screening in different database sources such as ZINC, NCI, ChemDB, PubChem, and Drugbank 2 1.1.1.267 additional information determination of the antimicrobial activities of various essential oils against different microbials using 35 plant essential oils (EOs), which have long been recognized for their antimicrobial properties. Essential oils of Zanbthoxylum bungeanum (ZB), Schizonepetae tenuifoliae (ST), Thymus quinquecostatus (TQ), Origanum vulgare (OV), and Eugenia caryophyllata (EC) display weak to medium inhibitory activity against DXR, with IC50 values of 0.078 mg/ml, 0.065 mg/ml, 0.059 mg/ml, 0.048 mg/ml, and 0.037 mg/ml, respectively. Dry roots or dry fruits are used for extraction. Cercis siliquastrum leaf extract strongly inhibits enzyme DXR. No effect by 0.5% DMSO on enzyme activity 2 1.1.1.267 additional information computational design of potent inhibitors for deoxyxylulose 5-phosphate reductoisomerase and prediction of pharmacokinetics and pharmacodynamics, active site binding, molecular docking, and complex-based pharmacophore modeling, binding structures, overview 2 1.1.1.267 N-hydroxy-N-[2-(3-hydroxy-3-oxido-3,4-dihydro-1H-2,3-benzoxaphosphinin-4-yl)ethyl]acetamide 12% inhibition at 0.1 mM 174556 1.1.1.267 NaCl 100 mM, 87% residual activity 42 1.1.1.267 NADP+ product inhibition 10 1.1.1.267 Ni2+ - 38 1.1.1.267 phosphate mono-((2S,3S)-3-fluoromethyl-2,4-dihydroxy-3-methyl-butyl) ester is a weak competitive inhibitor of DXR, most likely due to the steric hindrance caused by the substitution of a fluoromethylgroup for a hydroxyl group. Is not an irreversible inactivator (suicide inhibitor) for DXR, fails to act as a mechanism-based inactivator if the retroaldol/aldol mechanism is operative 151100 1.1.1.267 phosphoric acid mono-[2-(N-acetyl-N-hydroxy-amino)-ethyl]-ester - 62238 1.1.1.267 pyrimethamine - 761 1.1.1.267 quercetin - 137 1.1.1.267 quercetin 95.17% inhibition 137 1.1.1.267 quercetin 3-beta-D-glucoside - 259767 1.1.1.267 quercetin 3-beta-D-glucoside 23.75% inhibition 259767 1.1.1.267 quercetin 3-D-galactoside - 259768 1.1.1.267 quercetin 3-D-galactoside 23.21% inhibition 259768 1.1.1.267 quercitrin - 1936 1.1.1.267 quercitrin 21.79% inhibition 1936 1.1.1.267 Sarcopoterium spinosum plant extract - 143598 1.1.1.267 sulfamic acid 2-(N-formyl-N-hydroxy-amino)-ethyl ester - 62240 1.1.1.267 suramin hexasodium - 259762 1.1.1.267 theaflavin-3'-gallate non-competitive against 1-deoxy-D-xylulose 5-phosphate and un-competitive inhibitors with respect to NADPH 34589 1.1.1.267 theaflavin-3,3'-digallate non-competitive against 1-deoxy-D-xylulose 5-phosphate and un-competitive inhibitors with respect to NADPH 11507 1.1.1.267 theaflavin-3,3'-digallate strong inhibition of DXR, isolated from Camellia sinenesis 11507 1.1.1.267 theaflavin-3-gallate non-competitive against 1-deoxy-D-xylulose 5-phosphate and un-competitive inhibitors with respect to NADPH 123027 1.1.1.267 Thymol 26.5% inhibition of DXR 8200 1.1.1.267 Zn2+ - 14 1.1.1.267 [(1-isoquinolinylamino)methylene]-1,1-bisphosphonate 50% inhibition at 0.004 mM 122909 1.1.1.267 [(3,4-dichlorophenyl)([2-[hydroxy(methyl)amino]-2-oxoethyl]sulfanyl)methyl]phosphonic acid - 259703 1.1.1.267 [(5-phenylpyridin-2-yl)methyl]phosphonic acid - 89593 1.1.1.267 [(5Z)-5-(3,4-dihydroxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid inhibitor keeps its inhibition capacity in the presence of Triton X-100 215566 1.1.1.267 [(quinolin-2-yl)methyl]phosphonic acid - 259707 1.1.1.267 [1,1'-biphenyl]-3,4-diol - 259708 1.1.1.267 [1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonic acid - 89594 1.1.1.267 [1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonic acid conformation of inhibitor within the MtDXR active site (PDB ID 2Y1D) 89594 1.1.1.267 [1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonic acid inhibition of strain D2d 89594 1.1.1.267 [2-(1-hydroxy-6-oxo-1,6-dihydropyridin-2-yl)ethyl]phosphonic acid - 259710 1.1.1.267 [2-(2,3-dihydroxyphenyl)ethyl]phosphonic acid - 259711 1.1.1.267 [2-(3-hydroxy-4-methylphenyl)ethyl]phosphonic acid - 259713 1.1.1.267 [2-(3-methoxyanilino)-2-oxoethyl]phosphonic acid 17.8% inhibition at 0.25 mM 259714 1.1.1.267 [2-([1-[(2R)-2,3-dihydroxypropyl]piperidin-4-yl]oxy)phenyl](piperidin-1-yl)methanone - 259715 1.1.1.267 [2-[(3-bromophenyl)amino]-2-oxoethyl]phosphonic acid - 174557 1.1.1.267 [2-[(3-cyanophenyl)amino]-2-oxoethyl]phosphonic acid 20.0% inhibition 174565 1.1.1.267 [2-[(3-hydroxyphenyl)amino]-2-oxoethyl]phosphonic acid 43.9% inhibition 89588 1.1.1.267 [2-[(3-hydroxyphenyl)amino]-2-oxoethyl]phosphonic acid - 89588 1.1.1.267 [2-[(3-methoxyphenyl)amino]-2-oxoethyl]phosphonic acid 17.8% inhibition 89590 1.1.1.267 [2-[(3-methoxyphenyl)amino]-2-oxoethyl]phosphonic acid - 89590 1.1.1.267 [2-[(hydroxycarbamoyl)oxy]ethyl]phosphonic acid - 259716 1.1.1.267 [2-[acetyl(hydroxy)amino]ethyl]phosphonic acid 74% inhibition at 0.1 mM 259718 1.1.1.267 [3-(6-methyl-4,8-dioxo-1,3,6,2-dioxazaborocan-2-yl)propyl]phosphonic acid MIC90 = 0.063 mg/ml 259769 1.1.1.267 [3-(acetyl(hydroxy)amino)propyl]phosphonic acid 3-methylbutyl ester - 74716 1.1.1.267 [3-(acetyl(hydroxy)amino)propyl]phosphonic acid mono(2-naphthalen-1-yl-ethyl) ester - 74719 1.1.1.267 [3-(acetyl(hydroxy)amino)propyl]phosphonic acid mono(2-naphthalen-2-yl-ethyl) ester - 74718 1.1.1.267 [3-(acetyl(hydroxy)amino)propyl]phosphonic acid mono-n-butyl ester - 74715 1.1.1.267 [3-(acetyl(hydroxy)amino)propyl]phosphonic acid mono-n-propyl ester - 74714 1.1.1.267 [3-(acetyl(hydroxy)amino)propyl]phosphonic acid monomethyl ester - 74712 1.1.1.267 [3-(acetyl(hydroxy)amino)propyl]phosphonic acid monophenethyl ester - 74717 1.1.1.267 [3-(acetyl(hydroxy)amino)propyl]phosphonic monoethyl ester - 74713 1.1.1.267 [3-(N-acetyl-N-methyl-amino)propyl]-phosphonic acid - 62242 1.1.1.267 [3-(N-formyl-N-methyl-amino)-propyl]-phosphonic acid - 62241 1.1.1.267 [3-oxo-3-[(prop-2-yn-1-yl)amino]propyl]phosphonic acid 6.7% inhibition at 0.020 mM 259722 1.1.1.267 [3-[acetyl(hydroxy)amino]-1-(1,4-dihydropyridin-4-yl)propyl]phosphonic acid - 259724 1.1.1.267 [3-[acetyl(hydroxy)amino]-1-(2-bromophenyl)propyl]phosphonic acid 38% inhibition at 0.1 mM 89580 1.1.1.267 [3-[acetyl(hydroxy)amino]-1-(2-cyanophenyl)propyl]phosphonic acid 30% inhibition at 0.1 mM 174551 1.1.1.267 [3-[acetyl(hydroxy)amino]-1-(2-methylphenyl)propyl]phosphonic acid 55% inhibition at 0.1 mM 89582 1.1.1.267 [3-[acetyl(hydroxy)amino]-1-(3,4-dichlorophenyl)propyl]phosphonic acid - 89595 1.1.1.267 [3-[acetyl(hydroxy)amino]-1-(3,4-dichlorophenyl)propyl]phosphonic acid inhibition of strain D2d 89595 1.1.1.267 [3-[acetyl(hydroxy)amino]-1-(pyridin-3-yl)propyl]phosphonic acid - 10423 1.1.1.267 [3-[acetyl(hydroxy)amino]-1-(pyridin-4-yl)propyl]phosphonic acid - 10424 1.1.1.267 [3-[acetyl(hydroxy)amino]-1-phenylpropyl]phosphonic acid - 15380 1.1.1.267 [3-[acetyl(hydroxy)amino]-1-[2-(2-hydroxyethyl)phenyl]propyl]phosphonic acid 35% inhibition at 0.1 mM 89583 1.1.1.267 [3-[acetyl(hydroxy)amino]-1-[2-(hydroxymethyl)phenyl]propyl]phosphonic acid 36% inhibition at 0.1 mM 89581 1.1.1.267 [3-[acetyl(hydroxy)amino]-1-[2-(methoxymethyl)phenyl]propyl]phosphonic acid 30% inhibition at 0.1 mM 174555 1.1.1.267 [3-[acetyl(hydroxy)amino]-1-[2-(pyridin-3-yl)phenyl]propyl]phosphonic acid 20% inhibition at 0.1 mM 174552 1.1.1.267 [3-[acetyl(hydroxy)amino]-1-[2-(thiophen-2-yl)phenyl]propyl]phosphonic acid 30% inhibition at 0.1 mM 174554 1.1.1.267 [3-[acetyl(naphthalen-2-ylmethoxy)amino]propyl]phosphonic acid compound binds to both the NADPH and DXP sites, while whole-cell inhibitory activity is relatively poor 215568 1.1.1.267 [3-[formyl(hydroxy)amino]-1-(pyridin-3-yl)propyl]phosphonic acid - 10421 1.1.1.267 [3-[formyl(hydroxy)amino]-1-(pyridin-4-yl)propyl]phosphonic acid - 10422 1.1.1.267 [3-[formyl(hydroxy)amino]-1-phenylpropyl]phosphonic acid - 29052 1.1.1.267 [3-[hydroxy(3-phenylpropanoyl)amino]propyl]phosphonic acid compound binds to Dxr via a non-bisubstrate mechanism. The diethyl ester of [3-[hydroxy(3-phenylpropanoyl)amino]propyl]phosphonic acid inhibits Mycobacterium tuberculosis growth 215567 1.1.1.267 [4-(2-acetylanilino)-4-oxobutyl]phosphonic acid - 259727 1.1.1.267 [4-(2-fluoroanilino)-4-oxobutyl]phosphonic acid - 259728 1.1.1.267 [4-(hydroxyamino)-4-oxobutyl]phosphonic acid - 60296 1.1.1.267 [4-(methoxyamino)-4-oxobutyl]phosphonic acid - 259730 1.1.1.267 [4-[(3-bromophenyl)amino]-4-oxobutyl]phosphonic acid - 174558 1.1.1.267 [4-[(3-hydroxyphenyl)amino]-4-oxobutyl]phosphonic acid 49.2% inhibition 89589 1.1.1.267 [4-[(3-hydroxyphenyl)amino]-4-oxobutyl]phosphonic acid - 89589 1.1.1.267 [4-[2-(methanesulfonyl)anilino]-4-oxobutyl]phosphonic acid - 259734 1.1.1.267 [4-[acetyl(hydroxy)amino]butyl]phosphonic acid 80% inhibition at 0.1 mM 259735 1.1.1.267 [4-[hydroxy(methyl)amino]-4-oxobutyl]phosphonic acid - 259736 1.1.1.267 [4-[methoxy(methyl)amino]-4-oxobutyl]phosphonic acid - 259737 1.1.1.267 [5-[(3-bromophenyl)amino]-5-oxopentyl]phosphonic acid 26.8% inhibition 174564 1.1.1.267 [[(5-chloro-2-pyridinyl)amino]methylene]-1,1-bisphosphonate 50% inhibition at 0.007 mM 122910 1.1.1.267 [[(isoquinolin-1-yl)amino]methylene]bis(phosphonic acid) - 259738