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Literature summary extracted from

  • Li, Z.; Liu, Y.; Bai, X.; Deng, Q.; Wang, J.; Zhang, G.; Xiao, C.; Mei, Y.; Wang, Y.
    SAR studies on 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles as inhibitors of Mtb shikimate dehydrogenase for the development of novel antitubercular agents (2015), RSC Adv., 5, 97089-97101.
No PubMed abstract available

Application

EC Number Application Comment Organism
1.1.1.25 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

EC Number Inhibitors Comment Organism Structure
1.1.1.25 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole half-maximal inhibition at 0.023 mg/ml Mycobacterium tuberculosis
1.1.1.25 2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-4-carboxylic acid 31% inhibition at 0.2 mM Mycobacterium tuberculosis
1.1.1.25 2-[methyl[3-(trifluoromethyl)naphthalen-1-yl]amino]ethan-1-ol 49% inhibition at 0.2 mM Mycobacterium tuberculosis
1.1.1.25 3-(3-fluoropyridin-4-yl)-6-(phenoxymethyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole
-
 Mycobacterium tuberculosis
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 Mycobacterium tuberculosis
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 Mycobacterium tuberculosis
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 Mycobacterium tuberculosis
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 Mycobacterium tuberculosis
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 Mycobacterium tuberculosis
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 Mycobacterium tuberculosis
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 Mycobacterium tuberculosis
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 Mycobacterium tuberculosis
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 Mycobacterium tuberculosis
1.1.1.25 3-(4-fluorophenyl)-6-((2-naphthyloxy)methyl)-[1,2,4]triazolo-[3,4-b][1,3,4]thiadiazole
-
 Mycobacterium tuberculosis
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 Mycobacterium tuberculosis
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 Mycobacterium tuberculosis
1.1.1.25 3-ethyl-3,4-dihydro-2H-1-benzopyran 31% inhibition at 0.2 mM Mycobacterium tuberculosis
1.1.1.25 4-[(morpholin-4-yl)methyl]benzoic acid 31% inhibition at 0.2 mM Mycobacterium tuberculosis
1.1.1.25 5-(hex-1-yn-1-yl)furan-2-carboxylic acid 29% inhibition at 0.2 mM Mycobacterium tuberculosis
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
-
 Mycobacterium tuberculosis
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 Mycobacterium tuberculosis
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 Mycobacterium tuberculosis
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 Mycobacterium tuberculosis
1.1.1.25 methyl 3-hydroxy-1-benzothiophene-2-carboxylate 33% inhibition at 0.2 mM Mycobacterium tuberculosis
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 Mycobacterium tuberculosis
1.1.1.25 [2-[2-(dimethylamino)ethoxy]phenyl]methanol 45% inhibition at 0.2 mM Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.1.1.25 shikimate + NADP+ Mycobacterium tuberculosis
-
 3-dehydroshikimate + NADPH + H+
-
 ?
1.1.1.25 shikimate + NADP+ Mycobacterium tuberculosis H37Rv
-
 3-dehydroshikimate + NADPH + H+
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.1.1.25 Mycobacterium tuberculosis
-
 wild-tpe and clinical Mtb strains MDRTB and RDRTB exhibiting resistant profiles to isoniazid and rifampin
-
1.1.1.25 Mycobacterium tuberculosis H37Rv
-
 wild-tpe and clinical Mtb strains MDRTB and RDRTB exhibiting resistant profiles to isoniazid and rifampin
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.1.1.25 shikimate + NADP+
-
 Mycobacterium tuberculosis 3-dehydroshikimate + NADPH + H+
-
 ?
1.1.1.25 shikimate + NADP+
-
 Mycobacterium tuberculosis H37Rv 3-dehydroshikimate + NADPH + H+
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.1.1.25 AroE
-
 Mycobacterium tuberculosis
1.1.1.25 SDH
-
 Mycobacterium tuberculosis

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.1.1.25 25
-
 assay at Mycobacterium tuberculosis

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.1.1.25 9
-
 assay at Mycobacterium tuberculosis

Cofactor

EC Number Cofactor Comment Organism Structure
1.1.1.25 NADP+
-
 Mycobacterium tuberculosis