Application | Comment | Organism |
---|---|---|
drug development | shikimate dehydrogenase is an essential protein for the biosynthesis of the chorismate end product and is a highly promising therapeutic target, especially for the discovery and development of new-generation anti-tuberculosis agents | Mycobacterium tuberculosis |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
1,2,4-triazolo[3,4-b][1,3,4]thiadiazole | half-maximal inhibition at 0.023 mg/ml | Mycobacterium tuberculosis | |
2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-4-carboxylic acid | 31% inhibition at 0.2 mM | Mycobacterium tuberculosis | |
2-[methyl[3-(trifluoromethyl)naphthalen-1-yl]amino]ethan-1-ol | 49% inhibition at 0.2 mM | Mycobacterium tuberculosis | |
3-(3-fluoropyridin-4-yl)-6-(phenoxymethyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole | - |
Mycobacterium tuberculosis | |
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 | Mycobacterium tuberculosis | |
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 | Mycobacterium tuberculosis | |
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 | Mycobacterium tuberculosis | |
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 | Mycobacterium tuberculosis | |
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 | Mycobacterium tuberculosis | |
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 | Mycobacterium tuberculosis | |
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 | Mycobacterium tuberculosis | |
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 | Mycobacterium tuberculosis | |
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 | Mycobacterium tuberculosis | |
3-(4-fluorophenyl)-6-((2-naphthyloxy)methyl)-[1,2,4]triazolo-[3,4-b][1,3,4]thiadiazole | - |
Mycobacterium tuberculosis | |
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 | Mycobacterium tuberculosis | |
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 | Mycobacterium tuberculosis | |
3-ethyl-3,4-dihydro-2H-1-benzopyran | 31% inhibition at 0.2 mM | Mycobacterium tuberculosis | |
4-[(morpholin-4-yl)methyl]benzoic acid | 31% inhibition at 0.2 mM | Mycobacterium tuberculosis | |
5-(hex-1-yn-1-yl)furan-2-carboxylic acid | 29% inhibition at 0.2 mM | Mycobacterium tuberculosis | |
6-((2,4-dichlorophenoxy)methyl)-3-(3-fluoropyridin-4-yl)-[1,2,4]-triazolo[3,4-b][1,3,4]thiadiazole | - |
Mycobacterium tuberculosis | |
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 | Mycobacterium tuberculosis | |
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 | Mycobacterium tuberculosis | |
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 | Mycobacterium tuberculosis | |
methyl 3-hydroxy-1-benzothiophene-2-carboxylate | 33% inhibition at 0.2 mM | Mycobacterium tuberculosis | |
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 | Mycobacterium tuberculosis | |
[2-[2-(dimethylamino)ethoxy]phenyl]methanol | 45% inhibition at 0.2 mM | Mycobacterium tuberculosis |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
shikimate + NADP+ | Mycobacterium tuberculosis | - |
3-dehydroshikimate + NADPH + H+ | - |
? | |
shikimate + NADP+ | Mycobacterium tuberculosis H37Rv | - |
3-dehydroshikimate + NADPH + H+ | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mycobacterium tuberculosis | - |
wild-tpe and clinical Mtb strains MDRTB and RDRTB exhibiting resistant profiles to isoniazid and rifampin | - |
Mycobacterium tuberculosis H37Rv | - |
wild-tpe and clinical Mtb strains MDRTB and RDRTB exhibiting resistant profiles to isoniazid and rifampin | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
shikimate + NADP+ | - |
Mycobacterium tuberculosis | 3-dehydroshikimate + NADPH + H+ | - |
? | |
shikimate + NADP+ | - |
Mycobacterium tuberculosis H37Rv | 3-dehydroshikimate + NADPH + H+ | - |
? |
Synonyms | Comment | Organism |
---|---|---|
AroE | - |
Mycobacterium tuberculosis |
SDH | - |
Mycobacterium tuberculosis |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
25 | - |
assay at | Mycobacterium tuberculosis |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
9 | - |
assay at | Mycobacterium tuberculosis |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NADP+ | - |
Mycobacterium tuberculosis |