Application | Comment | Organism |
---|---|---|
drug development | the enzyme is an attractive target for the development of new antimicrobials and herbicides | Mycobacterium tuberculosis |
drug development | the enzyme is an attractive target for the development of new antimicrobials and herbicides | Streptomyces coelicolor |
drug development | the enzyme is an attractive target for the development of new antimicrobials and herbicides | Helicobacter pylori |
Crystallization (Comment) | Organism |
---|---|
DHQ2 in complex with inhibitors (4R,6R,7S)-4,6,7-trihydroxy-2-[(1Z)-prop-1-en-1-yl]-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid and (4R,6R,7S)-2-(1-cyclopropylethyl)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid, X-ray diffraction structure determination and analysis at 1.95 and 1.85 A resolution, respectively | Helicobacter pylori |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(1R,4R,5R)-1,4,5-trihydroxy-3-(3-nitrophenyl)cyclohex-2-ene-1-carboxylic acid | a competitive inhibitor | Helicobacter pylori | |
(1R,4R,5R)-1,4,5-trihydroxy-3-(3-nitrophenyl)cyclohex-2-ene-1-carboxylic acid | a competitive inhibitor | Mycobacterium tuberculosis | |
(1R,4R,5R)-1,4,5-trihydroxy-3-(3-phenoxyphenyl)cyclohex-2-ene-1-carboxylic acid | a competitive inhibitor | Helicobacter pylori | |
(1R,4R,5R)-1,4,5-trihydroxy-3-(3-phenoxyphenyl)cyclohex-2-ene-1-carboxylic acid | a competitive inhibitor | Mycobacterium tuberculosis | |
(1R,4R,5R)-1,4,5-trihydroxy-3-(thiophen-2-yl)cyclohex-2-ene-1-carboxylic acid | a competitive inhibitor | Helicobacter pylori | |
(1R,4R,5R)-1,4,5-trihydroxy-3-(thiophen-2-yl)cyclohex-2-ene-1-carboxylic acid | a competitive inhibitor | Mycobacterium tuberculosis | |
(1R,4R,5R)-1,4,5-trihydroxy-3-[(1E)-3-phenoxyprop-1-en-1-yl]cyclohex-2-ene-1-carboxylic acid | a competitive inhibitor | Helicobacter pylori | |
(1R,4R,5R)-1,4,5-trihydroxy-3-[(1E)-3-phenoxyprop-1-en-1-yl]cyclohex-2-ene-1-carboxylic acid | a competitive inhibitor | Mycobacterium tuberculosis | |
(1R,4R,5R)-1,4,5-trihydroxy-3-[3-(phenylsulfanyl)phenyl]cyclohex-2-ene-1-carboxylic acid | a competitive inhibitor | Helicobacter pylori | |
(1R,4R,5R)-1,4,5-trihydroxy-3-[3-(phenylsulfanyl)phenyl]cyclohex-2-ene-1-carboxylic acid | a competitive inhibitor | Mycobacterium tuberculosis | |
(1R,4S,5R)-3-(1-benzothiophen-2-ylmethoxy)-1,4,5-trihydroxycyclohex-2-ene-1-carboxylic acid | a competitive inhibitor | Helicobacter pylori | |
(1R,4S,5R)-3-(1-benzothiophen-2-ylmethoxy)-1,4,5-trihydroxycyclohex-2-ene-1-carboxylic acid | a competitive inhibitor | Mycobacterium tuberculosis | |
(3R,5R,6R)-3,5,6-trihydroxycyclohex-1-ene-1,3-dicarboxylic acid | a competitive inhibitor | Helicobacter pylori | |
(3R,5R,6R)-3,5,6-trihydroxycyclohex-1-ene-1,3-dicarboxylic acid | a competitive inhibitor | Mycobacterium tuberculosis | |
(4R,6R,7S)-2-(1-cyclopropylethyl)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Helicobacter pylori | |
(4R,6R,7S)-2-(1-cyclopropylethyl)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Mycobacterium tuberculosis | |
(4R,6R,7S)-2-(1-cyclopropylethyl)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Streptomyces coelicolor | |
(4R,6R,7S)-2-ethenyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Helicobacter pylori | |
(4R,6R,7S)-2-ethenyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Mycobacterium tuberculosis | |
(4R,6R,7S)-2-ethenyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Streptomyces coelicolor | |
(4R,6R,7S)-2-ethyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Helicobacter pylori | |
(4R,6R,7S)-2-ethyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Mycobacterium tuberculosis | |
(4R,6R,7S)-2-ethyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Streptomyces coelicolor | |
(4R,6R,7S)-2-[(1E)-2-cyclopropylprop-1-en-1-yl]-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Helicobacter pylori | |
(4R,6R,7S)-2-[(1E)-2-cyclopropylprop-1-en-1-yl]-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Mycobacterium tuberculosis | |
(4R,6R,7S)-2-[(1E)-2-cyclopropylprop-1-en-1-yl]-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Streptomyces coelicolor | |
(4R,6R,7S)-4,6,7-trihydroxy-2-(2-hydroxyethyl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Helicobacter pylori | |
(4R,6R,7S)-4,6,7-trihydroxy-2-(2-hydroxyethyl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Mycobacterium tuberculosis | |
(4R,6R,7S)-4,6,7-trihydroxy-2-(2-hydroxyethyl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Streptomyces coelicolor | |
(4R,6R,7S)-4,6,7-trihydroxy-2-(prop-2-en-1-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Helicobacter pylori | |
(4R,6R,7S)-4,6,7-trihydroxy-2-(prop-2-en-1-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Mycobacterium tuberculosis | |
(4R,6R,7S)-4,6,7-trihydroxy-2-(prop-2-en-1-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Streptomyces coelicolor | |
(4R,6R,7S)-4,6,7-trihydroxy-2-(propan-2-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Helicobacter pylori | |
(4R,6R,7S)-4,6,7-trihydroxy-2-(propan-2-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Mycobacterium tuberculosis | |
(4R,6R,7S)-4,6,7-trihydroxy-2-(propan-2-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Streptomyces coelicolor | |
(4R,6R,7S)-4,6,7-trihydroxy-2-methyl-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Helicobacter pylori | |
(4R,6R,7S)-4,6,7-trihydroxy-2-methyl-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Mycobacterium tuberculosis | |
(4R,6R,7S)-4,6,7-trihydroxy-2-methyl-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Streptomyces coelicolor | |
(4R,6R,7S)-4,6,7-trihydroxy-2-[(1Z)-prop-1-en-1-yl]-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Helicobacter pylori | |
(4R,6R,7S)-4,6,7-trihydroxy-2-[(1Z)-prop-1-en-1-yl]-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Mycobacterium tuberculosis | |
(4R,6R,7S)-4,6,7-trihydroxy-2-[(1Z)-prop-1-en-1-yl]-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Streptomyces coelicolor | |
(4R,6R,7S)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Helicobacter pylori | |
(4R,6R,7S)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Mycobacterium tuberculosis | |
(4R,6R,7S)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | - |
Streptomyces coelicolor | |
additional information | inhibitor design and synthesis, binding structure and inhibition mechanism, overview | Helicobacter pylori | |
additional information | inhibitor design and synthesis, binding structure and inhibition mechanism, overview | Mycobacterium tuberculosis | |
additional information | inhibitor design and synthesis, binding structure and inhibition mechanism, overview | Streptomyces coelicolor |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
3-dehydroquinate | Mycobacterium tuberculosis | - |
3-dehydroshikimate + H2O | - |
r | |
3-dehydroquinate | Streptomyces coelicolor | - |
3-dehydroshikimate + H2O | - |
r | |
3-dehydroquinate | Helicobacter pylori | - |
3-dehydroshikimate + H2O | - |
r |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Helicobacter pylori | - |
- |
- |
Mycobacterium tuberculosis | - |
- |
- |
Streptomyces coelicolor | - |
- |
- |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
3-dehydroquinate = 3-dehydroshikimate + H2O | DHQ2 catalyzes the reversible dehydration of 3-dehydroquinic acid to form 3-dehydroshikimic acid through anti elimination of water, with the loss of the more acidic pro-S hydrogen from C-2 of 3-dehydroquinate. The elimination proceeds by a stepwise E1CB mechanism involving an enol intermediate. In the first step, an essential tyrosine in the active site removes the pro-S hydrogen from C-2 of 1. The final step is the acid-catalyzed elimination of the C-1 hydroxy group, a reaction catalyzed by a histidine, which acts as a proton donor, reaction mechanism, overview | Mycobacterium tuberculosis | |
3-dehydroquinate = 3-dehydroshikimate + H2O | DHQ2 catalyzes the reversible dehydration of 3-dehydroquinic acid to form 3-dehydroshikimic acid through anti elimination of water, with the loss of the more acidic pro-S hydrogen from C-2 of 3-dehydroquinate. The elimination proceeds by a stepwise E1CB mechanism involving an enol intermediate. In the first step, an essential tyrosine in the active site removes the pro-S hydrogen from C-2 of 1. The final step is the acid-catalyzed elimination of the C-1 hydroxy group, a reaction catalyzed by a histidine, which acts as a proton donor, reaction mechanism, overview | Streptomyces coelicolor | |
3-dehydroquinate = 3-dehydroshikimate + H2O | DHQ2 catalyzes the reversible dehydration of 3-dehydroquinic acid to form 3-dehydroshikimic acid through anti elimination of water, with the loss of the more acidic pro-S hydrogen from C-2 of 3-dehydroquinate. The elimination proceeds by a stepwise E1CB mechanism involving an enol intermediate. In the first step, an essential tyrosine in the active site removes the pro-S hydrogen from C-2 of 1. The final step is the acid-catalyzed elimination of the C-1 hydroxy group, a reaction catalyzed by a histidine, which acts as a proton donor, reaction mechanism, overview | Helicobacter pylori |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
3-dehydroquinate | - |
Mycobacterium tuberculosis | 3-dehydroshikimate + H2O | - |
r | |
3-dehydroquinate | - |
Streptomyces coelicolor | 3-dehydroshikimate + H2O | - |
r | |
3-dehydroquinate | - |
Helicobacter pylori | 3-dehydroshikimate + H2O | - |
r |
Synonyms | Comment | Organism |
---|---|---|
DHQ2 | - |
Mycobacterium tuberculosis |
DHQ2 | - |
Streptomyces coelicolor |
DHQ2 | - |
Helicobacter pylori |
Type II dehydroquinase | - |
Mycobacterium tuberculosis |
Type II dehydroquinase | - |
Streptomyces coelicolor |
Type II dehydroquinase | - |
Helicobacter pylori |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
25 | - |
assay at | Mycobacterium tuberculosis |
25 | - |
assay at | Streptomyces coelicolor |
25 | - |
assay at | Helicobacter pylori |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.5 | - |
assay at | Mycobacterium tuberculosis |
7.5 | - |
assay at | Streptomyces coelicolor |
7.5 | - |
assay at | Helicobacter pylori |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.000054 | - |
(1R,4R,5R)-1,4,5-trihydroxy-3-(3-nitrophenyl)cyclohex-2-ene-1-carboxylic acid | pH not specified in the publication, temperature not specified in the publication | Mycobacterium tuberculosis | |
0.00012 | - |
(1R,4R,5R)-1,4,5-trihydroxy-3-[(1E)-3-phenoxyprop-1-en-1-yl]cyclohex-2-ene-1-carboxylic acid | pH not specified in the publication, temperature not specified in the publication | Mycobacterium tuberculosis | |
0.00013 | - |
(1R,4S,5R)-3-(1-benzothiophen-2-ylmethoxy)-1,4,5-trihydroxycyclohex-2-ene-1-carboxylic acid | pH not specified in the publication, temperature not specified in the publication | Helicobacter pylori | |
0.00025 | - |
(1R,4R,5R)-1,4,5-trihydroxy-3-(thiophen-2-yl)cyclohex-2-ene-1-carboxylic acid | pH not specified in the publication, temperature not specified in the publication | Mycobacterium tuberculosis | |
0.00038 | - |
(1R,4R,5R)-1,4,5-trihydroxy-3-[3-(phenylsulfanyl)phenyl]cyclohex-2-ene-1-carboxylic acid | pH not specified in the publication, temperature not specified in the publication | Mycobacterium tuberculosis | |
0.00049 | - |
(1R,4R,5R)-1,4,5-trihydroxy-3-(3-phenoxyphenyl)cyclohex-2-ene-1-carboxylic acid | pH not specified in the publication, temperature not specified in the publication | Helicobacter pylori | |
0.00054 | - |
(1R,4R,5R)-1,4,5-trihydroxy-3-(thiophen-2-yl)cyclohex-2-ene-1-carboxylic acid | pH not specified in the publication, temperature not specified in the publication | Helicobacter pylori | |
0.00094 | - |
(3R,5R,6R)-3,5,6-trihydroxycyclohex-1-ene-1,3-dicarboxylic acid | pH not specified in the publication, temperature not specified in the publication | Mycobacterium tuberculosis |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.00000084 | - |
pH 7.5, 25°C | Streptomyces coelicolor | (4R,6R,7S)-2-(1-cyclopropylethyl)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.0000011 | - |
pH 7.5, 25°C | Streptomyces coelicolor | (4R,6R,7S)-2-[(1E)-2-cyclopropylprop-1-en-1-yl]-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.000022 | - |
pH 7.5, 25°C | Streptomyces coelicolor | (4R,6R,7S)-4,6,7-trihydroxy-2-(2-hydroxyethyl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.000049 | - |
pH 7.5, 25°C | Mycobacterium tuberculosis | (4R,6R,7S)-4,6,7-trihydroxy-2-(2-hydroxyethyl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.000052 | - |
pH 7.5, 25°C | Mycobacterium tuberculosis | (4R,6R,7S)-2-ethenyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.000069 | - |
pH 7.5, 25°C | Mycobacterium tuberculosis | (4R,6R,7S)-2-ethyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.00009 | - |
pH 7.5, 25°C | Mycobacterium tuberculosis | (4R,6R,7S)-2-(1-cyclopropylethyl)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.000093 | - |
pH 7.5, 25°C | Streptomyces coelicolor | (4R,6R,7S)-4,6,7-trihydroxy-2-[(1Z)-prop-1-en-1-yl]-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.000097 | - |
pH 7.5, 25°C | Mycobacterium tuberculosis | (4R,6R,7S)-4,6,7-trihydroxy-2-[(1Z)-prop-1-en-1-yl]-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.00011 | - |
pH 7.5, 25°C | Mycobacterium tuberculosis | (4R,6R,7S)-2-[(1E)-2-cyclopropylprop-1-en-1-yl]-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.000122 | - |
pH 7.5, 25°C | Helicobacter pylori | (4R,6R,7S)-4,6,7-trihydroxy-2-(2-hydroxyethyl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.00019 | - |
pH 7.5, 25°C | Mycobacterium tuberculosis | (4R,6R,7S)-4,6,7-trihydroxy-2-(propan-2-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.0003 | - |
pH 7.5, 25°C | Mycobacterium tuberculosis | (4R,6R,7S)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.00032 | - |
pH 7.5, 25°C | Streptomyces coelicolor | (4R,6R,7S)-2-ethyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.00032 | - |
pH 7.5, 25°C | Helicobacter pylori | (4R,6R,7S)-2-ethyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.00035 | - |
pH 7.5, 25°C | Helicobacter pylori | (4R,6R,7S)-4,6,7-trihydroxy-2-[(1Z)-prop-1-en-1-yl]-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.0004 | - |
pH 7.5, 25°C | Mycobacterium tuberculosis | (4R,6R,7S)-4,6,7-trihydroxy-2-methyl-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.0006 | - |
pH 7.5, 25°C | Helicobacter pylori | (4R,6R,7S)-2-(1-cyclopropylethyl)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.00081 | - |
pH 7.5, 25°C | Streptomyces coelicolor | (4R,6R,7S)-2-ethenyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.00086 | - |
pH 7.5, 25°C | Mycobacterium tuberculosis | (4R,6R,7S)-4,6,7-trihydroxy-2-(prop-2-en-1-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.00108 | - |
pH 7.5, 25°C | Helicobacter pylori | (4R,6R,7S)-2-[(1E)-2-cyclopropylprop-1-en-1-yl]-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.00126 | - |
pH 7.5, 25°C | Helicobacter pylori | (4R,6R,7S)-2-ethenyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.0016 | - |
pH 7.5, 25°C | Helicobacter pylori | (4R,6R,7S)-4,6,7-trihydroxy-2-methyl-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.0018 | - |
pH 7.5, 25°C | Streptomyces coelicolor | (4R,6R,7S)-4,6,7-trihydroxy-2-(prop-2-en-1-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.0019 | - |
pH 7.5, 25°C | Streptomyces coelicolor | (4R,6R,7S)-4,6,7-trihydroxy-2-(propan-2-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.00315 | - |
pH 7.5, 25°C | Streptomyces coelicolor | (4R,6R,7S)-4,6,7-trihydroxy-2-methyl-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.0034 | - |
pH 7.5, 25°C | Helicobacter pylori | (4R,6R,7S)-4,6,7-trihydroxy-2-(propan-2-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.0097 | - |
pH 7.5, 25°C | Streptomyces coelicolor | (4R,6R,7S)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.034 | - |
pH 7.5, 25°C | Helicobacter pylori | (4R,6R,7S)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid | |
0.038 | - |
pH 7.5, 25°C | Helicobacter pylori | (4R,6R,7S)-4,6,7-trihydroxy-2-(prop-2-en-1-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid |