1.1.1.25 (3E)-3-[2-(4-bromophenyl)hydrazinylidene]piperidine-2,4,6-trione - 254466 1.1.1.25 (3R,3'R,4S,4'S,5R,5'R)-N,N'-(butane-1,4-diyl)bis(3,4,5-trihydroxycyclohex-1-ene-1-carboxamide) - 254475 1.1.1.25 (3R,3'R,4S,4'S,5R,5'R)-N,N'-(ethane-1,2-diyl)bis(3,4,5-trihydroxycyclohex-1-ene-1-carboxamide) - 254476 1.1.1.25 (3R,3'R,4S,4'S,5R,5'R)-N,N'-(propane-1,3-diyl)bis(3,4,5-trihydroxycyclohex-1-ene-1-carboxamide) - 254477 1.1.1.25 (3R,4S,5R)-3,4,5-trihydroxy-N-(3-hydroxypropyl)cyclohex-1-ene-1-carboxamide - 254479 1.1.1.25 (3R,4S,5R)-3,4,5-trihydroxy-N-(4-hydroxybutyl)cyclohex-1-ene-1-carboxamide - 254480 1.1.1.25 (3R,4S,5R)-3,4,5-trihydroxy-N-(5-hydroxypentyl)cyclohex-1-ene-1-carboxamide - 254481 1.1.1.25 (3R,4S,5R)-3,4,5-trihydroxy-N-(6-hydroxyhexyl)cyclohex-1-ene-1-carboxamide - 254482 1.1.1.25 (3R,4S,5R)-3,4,5-tri[(tert-butyldimethylsilyl)oxy]cyclohex-1-enecarboxylic acid - 254483 1.1.1.25 (4Z)-4-[2-(3-hydroxyphenyl)triazan-1-ylidene]-5-methyl-2-[(piperidin-1-yl)methyl]-2,4-dihydro-3H-pyrazol-3-one - 254541 1.1.1.25 (azepan-1-yl)(3-methyl-4,5-dinitrophenyl)methanone - 254612 1.1.1.25 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole half-maximal inhibition at 0.023 mg/ml 216165 1.1.1.25 1,3-benzodioxole-5-carbothioamide the compound shows higher affinity for the shikimate binding site than for the NADP+ binding site, mixed full inhibition mechanism versus shikimate, non-competitive full inhibition mechanism versus NADP+, interaction analysis and enzyme-bound structure, overview. 75% inhibition at 0.4 mM 254758 1.1.1.25 2,2'-bithiophene-5-carboxylic acid the inhibitor is identified by virtual screeening, 87% inhibition at 0.2 mM, competitive versus shikimate, uncompetitive versus NADP+. Flexible docking studies reveal that the inhibitor molecule makes interactions with catalytic residues 217296 1.1.1.25 2,2-bisepigallocatechin gallate about 50% inhibition at 0.0025 mM 217299 1.1.1.25 2,4-Dichlorophenoxyacetic acid - 5092 1.1.1.25 2,5-dimethyl-1,4-phenylene bis(trifluoroacetate) - 254943 1.1.1.25 2-(3,4-dihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3,5,7-triol - 254994 1.1.1.25 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxo-4H-1-benzopyran-3-yl 6-deoxy-alpha-L-mannopyranoside - 254995 1.1.1.25 2-(3,4-dihydroxyphenyl)ethyl 6-O-[(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]-beta-D-glucopyranoside - 254996 1.1.1.25 2-([2-([2-([2-(2,3-dimethylanilino)-2-oxoethyl]sulfanyl)-1,3-benzothiazol-6-yl]amino)2-oxoethyl]sulfanyl)-N-(2-naphthyl)acetamide IC50: 0.0029 mM, competitive inhibition with respect to shikimate, noncompetitive to NADP+, potent antibacterial activity 60524 1.1.1.25 2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-4-carboxylic acid 31% inhibition at 0.2 mM 216243 1.1.1.25 2-[methyl[3-(trifluoromethyl)naphthalen-1-yl]amino]ethan-1-ol 49% inhibition at 0.2 mM 216246 1.1.1.25 3,3,3-trifluoro-N-(2-nitrophenyl)-2-(trifluoromethyl)propanamide - 255311 1.1.1.25 3,5,7-trihydroxy-3'-(4-hydroxy-3-methoxyphenyl)-2'-(hydroxymethyl)-2,3,3',4'-tetrahydro-2'H,4H-[2,6'-bi-1-benzopyran]-4-one - 255320 1.1.1.25 3,5-dihydroxy-4-methylbenzoic acid - 255321 1.1.1.25 3,5-Dihydroxybenzoate moderate 5904 1.1.1.25 3-(2-naphthyloxy)-4-oxo-2-(trifluoromethyl)-4H-chromen-7-yl 3-chlorobenzoate IC50: 0.0039 mM, noncompetitive inhibition with respect to shikimate, competitive to NADP+ 60522 1.1.1.25 3-(3,4-dihydroxyphenyl)-2-[[(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy]propanoic acid - 255346 1.1.1.25 3-(3-fluoropyridin-4-yl)-6-(phenoxymethyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole - 216311 1.1.1.25 3-(4-bromophenyl)-6-((2,4-dichlorophenoxy)methyl)-[1,2,4]-triazolo[3,4-b][1,3,4]thiadiazole half-maximal inhibition at 0.0396 mg/ml 216315 1.1.1.25 3-(4-bromophenyl)-6-((2-methyl-4-chlorophenoxy)methyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole half-maximal inhibition at 0.0216 mg/ml 216314 1.1.1.25 3-(4-bromophenyl)-6-((4-chlorophenoxy)methyl)-[1,2,4]triazolo-[3,4-b][1,3,4]thiadiazole half-maximal inhibition at 0.0363 mg/ml 216316 1.1.1.25 3-(4-bromophenyl)-6-((4-fluorophenoxy)methyl)-[1,2,4]triazolo-[3,4-b][1,3,4]thiadiazole half-maximal inhibition at 0.0795 mg/ml 216317 1.1.1.25 3-(4-bromophenyl)-6-((4-methoxyphenoxy)methyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole half-maximal inhibition at 0.0120 mg/ml 216318 1.1.1.25 3-(4-bromophenyl)-6-((4-nitrophenoxy)methyl)-[1,2,4]triazolo-[3,4-b][1,3,4]thiadiazole half-maximal inhibition at 0.0586 mg/ml 216319 1.1.1.25 3-(4-chlorophenyl)-6-((2-naphthyloxy)methyl)-[1,2,4]triazolo-[3,4-b][1,3,4]thiadiazole half-maximal inhibition at 0.168 mg/ml 216320 1.1.1.25 3-(4-chlorophenyl)-6-((4-fluorophenoxy)methyl)-[1,2,4]triazolo-[3,4-b][1,3,4]thiadiazole half-maximal inhibition at 5.052 mg/ml 216321 1.1.1.25 3-(4-chlorophenyl)-6-((4-nitrophenoxy)methyl)-[1,2,4]triazolo-[3,4-b][1,3,4]thiadiazole half-maximal inhibition at 0.00937 mg/ml 216322 1.1.1.25 3-(4-fluorophenyl)-6-((2-naphthyloxy)methyl)-[1,2,4]triazolo-[3,4-b][1,3,4]thiadiazole - 216323 1.1.1.25 3-(4-fluorophenyl)-6-((4-methoxyphenoxy)methyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole half-maximal inhibition at 0.0663 mg/ml 216324 1.1.1.25 3-(4-hydroxyphenyl)-4-oxo-4H-1-benzopyran-7-yl hexopyranosiduronic acid - 255365 1.1.1.25 3-(beta-naphthylmethyl)-6-((4-nitrophenoxy)methyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole half-maximal inhibition at 0.0407 mg/ml 216330 1.1.1.25 3-ethyl-3,4-dihydro-2H-1-benzopyran 31% inhibition at 0.2 mM 216410 1.1.1.25 3-hydroxy-4-(methoxycarbonyl)-2,5-dimethylphenyl 3-formyl-2,4-dihydroxy-6-methylbenzoate - 255407 1.1.1.25 3-[[(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy]-1,4,5-trihydroxycyclohexane-1-carboxylic acid - 255493 1.1.1.25 4,4'-methylenebis(2,6-dibromo-3,5-dihydroxybenzoic acid) - 255520 1.1.1.25 4-hydroxy-6-methyl-2-oxo-1-(2-phenylethyl)-1,2-dihydropyridine-3-carbaldehyde - 255605 1.1.1.25 4-[(morpholin-4-yl)methyl]benzoic acid 31% inhibition at 0.2 mM 216520 1.1.1.25 4-[[(E)-(2-ethoxy-6-methyl-4-oxo-2H-1-benzopyran-3(4H)-ylidene)methyl]amino]-2-hydroxybenzoic acid - 255667 1.1.1.25 5-(6-hydroxy-1-benzofuran-2-yl)-2-[(1E)-3-methylbut-1-en-1-yl]benzene-1,3-diol - 255695 1.1.1.25 5-(hex-1-yn-1-yl)furan-2-carboxylic acid 29% inhibition at 0.2 mM 216588 1.1.1.25 5-[4-(1H-imidazol-2-ylcarbonyl)phenyl]thiophene-2-carboxylic acid the compound shows higher affinity for the shikimate binding site than for the NADP+ binding site, uncompetitive full inhibition versus shikimate and mixed full inhibition versus NADP+, interaction analysis and enzyme-bound structure, overview. 98% inhibition at 0.4 mM 255726 1.1.1.25 5-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione - 255739 1.1.1.25 6-((2,4-dichlorophenoxy)methyl)-3-(3-fluoropyridin-4-yl)-[1,2,4]-triazolo[3,4-b][1,3,4]thiadiazole - 216609 1.1.1.25 6-((4-bromophenoxy)methyl)-3-(4-bromophenyl)-[1,2,4]triazolo-[3,4-b][1,3,4]thiadiazole half-maximal inhibition at 0.0144 mg/ml 216610 1.1.1.25 6-((4-bromophenoxy)methyl)-3-(4-chlorophenyl)-[1,2,4]triazolo-[3,4-b][1,3,4]thiadiazole half-maximal inhibition at 0.00682 mg/ml 216611 1.1.1.25 6-((4-fluorophenoxy)methyl)-3-(beta-naphthylmethyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole half-maximal inhibition at 0.0277 mg/ml 216612 1.1.1.25 6-(2,6-dichlorophenoxy) pyridin-3-amine 60% inhibition at 0.4 mM 255752 1.1.1.25 6-amino-1,2,3,4-tetrahydronaphthalen-1-one the compound presents a higher affinity for NADP+ binding site than for shikimate binding, mixed partial inhibition mechanism versus NADP+ and mixed full versus shikimate, interaction analysis and enzyme-bound structure, overview. 91% inhibition at 0.4 m 255762 1.1.1.25 6-hydroxy-1-benzofuran-3(2H)-one - 255778 1.1.1.25 6-hydroxy-2,3-dihydrobenzo[b]furan-3-one the inhibitor is identified by virtual screeening, 99% inhibition at 0.2 mM, mixed-type inhibition versus shikimate, uncompetitive versus NADP+. Flexible docking studies reveal that the inhibitor molecule makes interactions with catalytic residues 217298 1.1.1.25 6-hydroxy-7-methyl-1-benzofuran-3(2H)-one mixed partial inhibition mechanism versus NADP+ and shikimate, interaction analysis and enzyme bound structure, overview. 98% inhibition at 0.4 mM 255780 1.1.1.25 7-hydroxy-2,2,8-trimethyl-2,3-dihydro-4H-1-benzopyran-4-one - 255816 1.1.1.25 7-hydroxy-2,2,8-trimethyl-2,3-dihydro-4H-chromen-4-one the inhibitor is identified by virtual screeening, 87% inhibition at 0.2 mM, competitive versus shikimate, uncompetitive versus NADP+. Flexible docking studies reveal that the inhibitor molecule makes interactions with catalytic residues 217297 1.1.1.25 ajmalicine (19alpha)-16,17-didehydro-19-methyloxayohimban-16-carboxylic acid methyl ester, from Rauwolfia serpentina leaves and roots, interacting residues are Asp131 and Arg130 254205 1.1.1.25 arsenite - 397 1.1.1.25 aurintricarboxylic acid lower inhibitry potency, about 25% inhibition at 0.0025 mM 1818 1.1.1.25 baicalein about 25% inhibition at 0.0025 mM 1102 1.1.1.25 Borate - 1395 1.1.1.25 butyl 2-([3-(2-naphthyloxy)4-oxo-2-(trifluoromethyl)4H-chromen-7-yl]oxy)propanoate IC50: 0.0134 mM, noncompetitive inhibition with respect to shikimate, competitive to NADP+, potent antibacterial activity 60523 1.1.1.25 cardiolipin lower inhibitry potency, about 25% inhibition at 0.0025 mM 813 1.1.1.25 Cd2+ 500 nM 52 1.1.1.25 CdSO4 - 4508 1.1.1.25 Cu2+ - 19 1.1.1.25 curcumin IC50: 0.0154 mM, noncompetitive inhibition with respect to shikimate and NADP+ 696 1.1.1.25 curcumin a noncompetitive inhibitor 696 1.1.1.25 CuSO4 - 263 1.1.1.25 cyclopropyl(5-hydroxy-1-benzofuran-3-yl)methanone 32% inhibition at 0.4 mM 255901 1.1.1.25 dianthrol about 50% inhibition at 0.0025 mM 217302 1.1.1.25 diethylenetriamine pentaacetic acid lower inhibitry potency, about 25% inhibition at 0.0025 mM 162991 1.1.1.25 ebselen lower inhibitry potency, about 25% inhibition at 0.0025 mM 2514 1.1.1.25 ellagic acid about 50% inhibition at 0.0025 mM 1279 1.1.1.25 epicatechin gallate inhibits the AroE domain of the bifunctional dehydroquinate dehydratase-shikimate dehydrogenase (DHQ-SDH) from Arabidopsis thaliana 3466 1.1.1.25 epicatechin gallate over 75% inhibition at 0.0025 mM 3466 1.1.1.25 epigallocatechin gallate inhibits the AroE domain of the bifunctional dehydroquinate dehydratase-shikimate dehydrogenase (DHQ-SDH) from Arabidopsis thaliana 1234 1.1.1.25 epigallocatechin gallate over 75% inhibition at 0.0025 mM 1234 1.1.1.25 epigallocatechin gallate - 1234 1.1.1.25 epigallocatechin-3,5-digallate about 50% inhibition at 0.0025 mM 143708 1.1.1.25 epitheaflavin monogallate about 50% inhibition at 0.0025 mM 69249 1.1.1.25 ethyl 5-(1H-pyrazol-3-yl)thiophene-2-carboxylate 28% inhibition at 0.4 mM 255917 1.1.1.25 guaiacol - 359 1.1.1.25 Hg2+ - 33 1.1.1.25 HgCl2 complete inhibition at concentration 0.05 mM 110 1.1.1.25 hydroquinone lower inhibitry potency, about 25% inhibition at 0.0025 mM 442 1.1.1.25 iodoacetate - 93 1.1.1.25 iodoacetate slight 93 1.1.1.25 limonin 7,16-dioxo-7,16-dideoxylimondiol, from Citrus sp. fruits, interacting residues are Thr75, Thr78, Val71, Gln101, and Pro103 4616 1.1.1.25 maesaquinone diacetate IC50: 0.0035 mM, noncompetitive inhibition with respect to shikimate and NADP+ 60525 1.1.1.25 merbromin lower inhibitry potency, about 25% inhibition at 0.0025 mM 39883 1.1.1.25 Metal ions - 31112 1.1.1.25 methyl 3-hydroxy-1-benzothiophene-2-carboxylate 33% inhibition at 0.2 mM 216813 1.1.1.25 additional information antibacterial activity of inhibitors, overview 2 1.1.1.25 additional information no inhibition of paralogue HI0607 by EDTA 2 1.1.1.25 additional information not inhibitory: quinate; not inhibitory: quinate 2 1.1.1.25 additional information inhibitor screening 2 1.1.1.25 additional information screening for polyphenolc enzyme inhibitors, overview 2 1.1.1.25 additional information screening for polyphenolc enzyme inhibitors, overview. No inhibition by gallic acid, epigallocatechin and epicatechin 2 1.1.1.25 additional information no inhibition by curcumin 2 1.1.1.25 additional information structure-activity relationship studies on 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles as inhibitors of shikimate dehydrogenase, 3,6-disubstituted triazolothiadiazoles synthesis, overview. The compounds exhibit cytotoxicity against Vero and Hep-G2 cellss, IC50 and MIC values 2 1.1.1.25 additional information structure-based inhibitor design, small-molecule library screening, inhibition mechanism analysis 2 1.1.1.25 additional information integrated virtual screening/molecular docking-based virtual screening, and antibacterial test for identification of enzyme inhibitors, screening of ZINC database. The HpSDH active site prefers to accommodate amphipathic and polar inhibitors that consist of an aromatic core as well as a number of oxygen-rich polar/charged substituents such as hydroxyl, carbonyl, and carboxyl groups. Subpockets 1- and 2-specific inhibitors exhibit a generally higher activity than subpocket 3-specific inhibitors. Molecular dynamics simulations revealed an intense nonbonded network of hydrogen bonds, Pi-Pi stacking, and van der Waals contacts at the tightly packed complex interfaces of active-site subpockets with their cognate inhibitors, conferring strong stability and specificity to these complex systems. Binding energetic analysis demonstrates that the identified potent inhibitors can target their cognate subpockets with an effective selectivity over noncognate ones. Determination of MIC values of the compounds against Helicobacter strains ATCC43504 and ATCC700392, and structural and energetic analysis of subpocket-inhibitor interactions, overview 2 1.1.1.25 additional information ten clinical isolates of Acinetobacter baumannii are used for inhibitor screening. Ajmalicine, strictamin, and limonin exhibit promising binding towards multiple drug targets of Acinetobacter baumannii in comparison with the binding between standard drugs and their targets. The tested isolates exhibit resistance to antibiotics clinafloxacin, imipenem and polymyxin-E, and the herbal preparations (crude extracts) demonstrate a significant antibacterial potential. Docking study and molecular dynamic simulations, model refinement and validation, overview. Acinetobacter baumannii exhibits resistance to a broad range of antibiotics due to the presence of a protective capsule, lipopolysaccharide, AbaR resistance islands, OmpA, efflux pumps, biofilms formation, and other mechanisms. Evaluation of drug targets in Acinetobacter baumannii. The toxicity prediction for ajmalicine (Rauvolfia serpentina) and strictamin (Alstonia scholaris) are predicted to be non-carcinogenic in both mouse and rat models making them potential leads 2 1.1.1.25 additional information simulations of shikimate dehydrogenase from Mycobacterium tuberculosis in complex with 3-dehydroshikimate and NADPH for MtbSDH inhibition strategy, overview. Rational design of hybrid MtbSDH inhibitors able to bind in both the substrate (DHS) and cofactor (NADPH) pockets 2 1.1.1.25 additional information synthesis, biological activity and molecular modelling studies of shikimic acid derivatives as inhibitors of the shikimate dehydrogenase enzyme of Escherichia coli, evaluation for in vitro SDH inhibition and antibacterial activity against Escherichia coli, molecular docking studies, overview. All tested compounds are mixed-type inhibitors, diamide derivatives display more inhibitory activity than synthesised monoamides 2 1.1.1.25 N-ethylmaleimide - 49 1.1.1.25 N-methyl-N-(quinolin-6-ylmethyl)amine 63% inhibition at 0.4 mM 256153 1.1.1.25 N-[2,2-dimethyl-6-(1-methyldioxidan-1-ium-1-yl)-3,4-dihydro-2H-1-benzopyran-4-yl]-N2-methyl-N2-[(pyridin-2-yl)methyl]glycinamide 34% inhibition at 0.4 mM 256174 1.1.1.25 NADP+ product inhibition, competitive versus NADPH, noncompetitive versus 3-dehydroshikimate 10 1.1.1.25 NH4+ - 54 1.1.1.25 nordihydroguaiaretic acid lower inhibitry potency, about 25% inhibition at 0.0025 mM 926 1.1.1.25 p-chloromercuribenzoate - 43 1.1.1.25 p-chloromercuribenzoate biphasic inhibition: first rapid inhibition leading to loss of 70% activity, then within 5 min loss of the remaining 30% activity, inhibition can be partially hindered by thiols and chloride 43 1.1.1.25 p-hydroxymercuribenzoate moderate 98 1.1.1.25 protocatechuic acid - 1934 1.1.1.25 protocatechuic acid moderate 1934 1.1.1.25 protocatechuic acid competitive inhibition 1934 1.1.1.25 purpurogallin about 50% inhibition at 0.0025 mM 5210 1.1.1.25 pyridoxine lower inhibitry potency, about 25% inhibition at 0.0025 mM 1051 1.1.1.25 pyrogallin about 50% inhibition at 0.0025 mM 69245 1.1.1.25 quercetin about 25% inhibition at 0.0025 mM 137 1.1.1.25 SDS nearly complete inactivation of AroE at 0.02% 124 1.1.1.25 shikimate product inhibition, noncompetitive versus NADPH, competitive versus 3-dehydroshikimate 352 1.1.1.25 shikimate shikimate synthesis decreases with increasing shikimate concentration. The relative activity halves at about 1.4 mM shikimate; shikimate synthesis decreases with increasing shikimate concentration. The relative activity halves at about 1.4 mM shikimate 352 1.1.1.25 strictamin akuammilan-17-oic acid methyl ester, from Alstonia scholaris leaves, interacting residues are Tyr129, Gln126, and Leu125 254206 1.1.1.25 taxifolin about 25% inhibition at 0.0025 mM 3233 1.1.1.25 theaflavanin about 25% inhibition at 0.0025 mM 206460 1.1.1.25 theaflavin monogallate about 50% inhibition at 0.0025 mM 69246 1.1.1.25 theaflavin-3,3-digallate about 25% inhibition at 0.0025 mM 217300 1.1.1.25 Zn2+ - 14 1.1.1.25 Zn2+ 0.005 mM 14 1.1.1.25 ZnCl2 - 271 1.1.1.25 [2,2'-bithiophene]-5-carboxylic acid - 256353 1.1.1.25 [2-[2-(dimethylamino)ethoxy]phenyl]methanol 45% inhibition at 0.2 mM 216115 1.1.1.25 [4-(4-methylperhydro-1,4-diazepin-1-yl)phenyl]methanol 67% inhibition at 0.4 mM 256382