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Literature summary for 2.7.1.40 extracted from

  • Labriere, C.; Gong, H.; Finlay, B.B.; Reiner, N.E.; Young, R.N.
    Further investigation of inhibitors of MRSA pyruvate kinase towards the conception of novel antimicrobial agents (2017), Eur. J. Med. Chem., 125, 1-13 .
    View publication on PubMed
Search for more literature for 2.7.1.40

Application

Application Comment Organism
drug development structural features of MRSA that are distinct from the human enzyme features makes the Staphylococcus enzyme an antimicrobial target Staphylococcus aureus

Inhibitors

Inhibitors Comment Organism Structure
(2E)-1,3-bis(6-bromo-1H-indol-2-yl)prop-2-en-1-one 6% inhibition at 0.001 mM Staphylococcus aureus
(2E)-1-(3-bromo-2-hydroxyphenyl)-3-(6-bromo-1H-indol-2-yl)prop-2-en-1-one 41% inhibition at 0.001 mM Staphylococcus aureus
(2E)-1-(4-bromo-2-hydroxyphenyl)-3-(1H-indol-2-yl)prop-2-en-1-one
-
 Staphylococcus aureus
(2E)-1-(4-bromo-2-hydroxyphenyl)-3-(6-bromo-1H-indol-2-yl)prop-2-en-1-one
-
 Staphylococcus aureus
(2E)-1-(5-bromo-1H-indol-2-yl)-3-(6-bromo-1H-indol-2-yl)prop-2-en-1-one 21% inhibition at 0.001 mM Staphylococcus aureus
(2E)-1-(5-bromo-2-hydroxyphenyl)-3-(1H-indol-2-yl)prop-2-en-1-one 10% inhibition at 0.001 mM Staphylococcus aureus
(2E)-1-(5-bromo-2-hydroxyphenyl)-3-(6-bromo-1H-indol-2-yl)prop-2-en-1-one 15% inhibition at 0.001 mM Staphylococcus aureus
(2E)-1-(6-bromo-1H-indol-2-yl)-3-(1H-indol-2-yl)prop-2-en-1-one
-
 Staphylococcus aureus
(2E)-1-(6-bromo-1H-indol-2-yl)-3-(5-bromo-2-methoxyphenyl)prop-2-en-1-one
-
 Staphylococcus aureus
(2E)-2-[(5-bromo-2-methoxyphenyl)methylidene]-2,3,4,9-tetrahydro-1H-carbazol-1-one 22% inhibition at 0.001 mM Staphylococcus aureus
(2E)-3-(3-bromo-2-hydroxyphenyl)-1-(6-bromo-1H-indol-2-yl)prop-2-en-1-one
-
 Staphylococcus aureus
(2E)-3-(4-bromo-2-hydroxyphenyl)-1-(6-bromo-1H-indol-2-yl)prop-2-en-1-one
-
 Staphylococcus aureus
(2E)-3-(5-bromo-1H-indol-3-yl)-1-(1H-indol-2-yl)prop-2-en-1-one
-
 Staphylococcus aureus
(2E)-3-(5-bromo-2-hydroxyphenyl)-1-(1H-indol-2-yl)prop-2-en-1-one
-
 Staphylococcus aureus
(2E)-3-(5-bromo-2-hydroxyphenyl)-1-(6-bromo-1H-indol-2-yl)prop-2-en-1-one
-
 Staphylococcus aureus
(2E)-3-(6-bromo-1H-indol-2-yl)-1-(1H-indol-2-yl)prop-2-en-1-one 38% inhibition at 0.001 mM Staphylococcus aureus
(2E)-3-(6-bromo-1H-indol-2-yl)-1-(2-hydroxyphenyl)prop-2-en-1-one
-
 Staphylococcus aureus
(2E)-3-(6-bromo-1H-indol-3-yl)-1-(1H-indol-2-yl)prop-2-en-1-one 45% inhibition at 0.001 mM Staphylococcus aureus
(2E)-3-(6-bromo-1H-indol-3-yl)-1-(1H-indol-3-yl)prop-2-en-1-one 28% inhibition at 0.001 mM Staphylococcus aureus
1-(6-bromo-1-benzothiophen-2-yl)-2-(4-bromophenyl)ethan-1-one 43% inhibition at 0.001 mM Staphylococcus aureus
1-(6-bromo-1H-indol-2-yl)-2-(4-bromophenyl)ethan-1-one
-
 Staphylococcus aureus
2-(3-bromo-2-hydroxyphenyl)-1-(6-bromo-1H-indol-2-yl)ethan-1-one
-
 Staphylococcus aureus
2-(4-bromophenyl)-1-(1H-indol-2-yl)ethan-1-one 41% inhibition at 0.001 mM Staphylococcus aureus
2-(5-bromo-1H-benzimidazol-2-yl)-1-(5-bromo-1H-indol-2-yl)ethan-1-one
-
 Staphylococcus aureus
2-(5-bromo-1H-benzimidazol-2-yl)-1-(5-bromo-2-hydroxyphenyl)ethan-1-one
-
 Staphylococcus aureus
2-(5-bromo-1H-benzimidazol-2-yl)-1-(6-bromo-1H-indol-2-yl)ethan-1-one
-
 Staphylococcus aureus
2-(5-bromo-2-hydroxyphenyl)-1-(1H-indol-2-yl)ethan-1-one 28% inhibition at 0.001 mM Staphylococcus aureus
2-(6-bromo-1,3-benzothiazol-2-yl)-1-(1-methyl-1H-indol-2-yl)ethan-1-one 41% inhibition at 0.001 mM Staphylococcus aureus
2-(6-bromo-1,3-benzothiazol-2-yl)-1-(1H-indol-2-yl)ethan-1-one
-
 Staphylococcus aureus
2-(6-bromo-1,3-benzothiazol-2-yl)-1-(3-bromo-2-hydroxyphenyl)ethan-1-one
-
 Staphylococcus aureus
2-(6-bromo-1,3-benzothiazol-2-yl)-1-(3-bromo-2-methoxyphenyl)ethan-1-one 22% inhibition at 0.001 mM Staphylococcus aureus
2-(6-bromo-1,3-benzothiazol-2-yl)-1-(3-chloro-2-hydroxyphenyl)ethan-1-one 43% inhibition at 0.001 mM Staphylococcus aureus
2-(6-bromo-1,3-benzothiazol-2-yl)-1-(4-bromo-2-hydroxyphenyl)ethan-1-one
-
 Staphylococcus aureus
2-(6-bromo-1,3-benzothiazol-2-yl)-1-(5-bromo-1H-indol-2-yl)ethan-1-one
-
 Staphylococcus aureus
2-(6-bromo-1,3-benzothiazol-2-yl)-1-(5-bromo-2-methoxyphenyl)ethan-1-one
-
 Staphylococcus aureus
2-bromo-6-[[(6-bromo-1,3-benzothiazol-2-yl)amino]methyl]phenol 17% inhibition at 0.001 mM Staphylococcus aureus
2-[5-(5-bromo-2-methoxyphenyl)-1,3,4-oxadiazol-2-yl]-1H-indole 19% inhibition at 0.001 mM Staphylococcus aureus
2-[6-(5-bromo-2-methoxyphenyl)pyridin-2-yl]-1H-indole 6% inhibition at 0.001 mM Staphylococcus aureus
4-bromo-2-[(E)-[(6-bromo-1,3-benzothiazol-2-yl)imino]methyl]phenol 41% inhibition at 0.001 mM Staphylococcus aureus
4-bromo-2-[2-(6-bromo-1H-indol-2-yl)pyridin-4-yl]phenol 41% inhibition at 0.001 mM Staphylococcus aureus
4-bromo-2-[5-(1H-indol-2-yl)-1,3,4-oxadiazol-2-yl]phenol 8% inhibition at 0.001 mM Staphylococcus aureus
5-bromo-2-(4-bromophenyl)-1H-indole 21% inhibition at 0.001 mM Staphylococcus aureus
5-bromo-2-(6-bromo-1,3-benzothiazol-2-yl)-1H-isoindole-1,3(2H)-dione 34% inhibition at 0.001 mM Staphylococcus aureus
5-bromo-3-(4-bromophenyl)-1H-indole 20% inhibition at 0.001 mM Staphylococcus aureus
5-bromo-N-(5-bromo-1,3-benzothiazol-2-yl)-1H-indole-2-carboxamide
-
 Staphylococcus aureus
5-bromo-N-(6-bromo-1,3-benzothiazol-2-yl)-2-hydroxy-N-methylbenzamide 5% inhibition at 0.001 mM Staphylococcus aureus
5-bromo-N-(6-bromo-1,3-benzothiazol-2-yl)-2-hydroxybenzamide
-
 Staphylococcus aureus
6-bromo-3-(4-bromophenyl)-1H-indole
-
 Staphylococcus aureus
bromodeoxytopsentin
-
 Staphylococcus aureus
cis-3-4-dihydrohamacanthin B
-
 Staphylococcus aureus
additional information synthesis and evaluation of several series of compounds as inhibitors of methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase. Structure-activity analysis, overview. (2E)-3-(5-bromo-1H-indol-3-yl)-1-(1H-indol-3-yl)prop-2-en-1-one and (2E)-1-(3-bromo-2-hydroxyphenyl)-3-(1H-indol-2-yl)prop-2-en-1-one are not inhibitory Staphylococcus aureus
N'-[(1E)-1-(1H-benzimidazol-2-yl)ethylidene]-5-bromo-2-hydroxybenzohydrazide
-
 Staphylococcus aureus
N'-[(1E)-1-(1H-benzimidazol-2-yl)propylidene]-5-bromo-2-hydroxybenzohydrazide
-
 Staphylococcus aureus
N-(1,3-benzothiazol-2-yl)-2-hydroxy-5-sulfanylbenzamide 13% inhibition at 0.001 mM Staphylococcus aureus
N-(5-bromo-1,3-benzothiazol-2-yl)-1H-indole-2-carboxamide
-
 Staphylococcus aureus
N-(5-bromo-1,3-benzothiazol-2-yl)-2-hydroxy-5-sulfanylbenzamide 48% inhibition at 0.001 mM Staphylococcus aureus
N-(6-bromo-1,3-benzothiazol-2-yl)-2-hydroxybenzamide 65% inhibition at 0.001 mM Staphylococcus aureus

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Staphylococcus aureus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ADP + phosphoenolpyruvate Staphylococcus aureus
-
 ATP + pyruvate
-
 ?
ADP + phosphoenolpyruvate Staphylococcus aureus ATCC 29213
-
 ATP + pyruvate
-
 ?

Organism

Organism UniProt Comment Textmining
Staphylococcus aureus
-
 MRSA
-
Staphylococcus aureus ATCC 29213
-
 MRSA
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ADP + phosphoenolpyruvate
-
 Staphylococcus aureus ATP + pyruvate
-
 ?
ADP + phosphoenolpyruvate
-
 Staphylococcus aureus ATCC 29213 ATP + pyruvate
-
 ?

Subunits

Subunits Comment Organism
homotetramer 4 * 50000-60000 Staphylococcus aureus

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000002
-
 pH and temperature not specified in the publication Staphylococcus aureus 2-(5-bromo-1H-benzimidazol-2-yl)-1-(6-bromo-1H-indol-2-yl)ethan-1-one
0.000003
-
 pH and temperature not specified in the publication Staphylococcus aureus 2-(5-bromo-1H-benzimidazol-2-yl)-1-(5-bromo-1H-indol-2-yl)ethan-1-one
0.000003
-
 pH and temperature not specified in the publication Staphylococcus aureus 5-bromo-N-(6-bromo-1,3-benzothiazol-2-yl)-2-hydroxybenzamide
0.000004
-
 pH and temperature not specified in the publication Staphylococcus aureus 2-(6-bromo-1,3-benzothiazol-2-yl)-1-(3-chloro-2-hydroxyphenyl)ethan-1-one
0.000005
-
 pH and temperature not specified in the publication Staphylococcus aureus (2E)-1-(6-bromo-1H-indol-2-yl)-3-(1H-indol-2-yl)prop-2-en-1-one
0.000008
-
 pH and temperature not specified in the publication Staphylococcus aureus (2E)-1-(6-bromo-1H-indol-2-yl)-3-(5-bromo-2-methoxyphenyl)prop-2-en-1-one
0.000008
-
 pH and temperature not specified in the publication Staphylococcus aureus 2-(6-bromo-1,3-benzothiazol-2-yl)-1-(5-bromo-2-methoxyphenyl)ethan-1-one
0.000008
-
 pH and temperature not specified in the publication Staphylococcus aureus 5-bromo-N-(5-bromo-1,3-benzothiazol-2-yl)-1H-indole-2-carboxamide
0.00001
-
 pH and temperature not specified in the publication Staphylococcus aureus 1-(6-bromo-1H-indol-2-yl)-2-(4-bromophenyl)ethan-1-one
0.000011
-
 pH and temperature not specified in the publication Staphylococcus aureus 2-(5-bromo-1H-benzimidazol-2-yl)-1-(5-bromo-2-hydroxyphenyl)ethan-1-one
0.000011
-
 pH and temperature not specified in the publication Staphylococcus aureus 2-(6-bromo-1,3-benzothiazol-2-yl)-1-(1H-indol-2-yl)ethan-1-one
0.000012
-
 pH and temperature not specified in the publication Staphylococcus aureus 2-(4-bromophenyl)-1-(1H-indol-2-yl)ethan-1-one
0.000014
-
 pH and temperature not specified in the publication Staphylococcus aureus (2E)-3-(4-bromo-2-hydroxyphenyl)-1-(6-bromo-1H-indol-2-yl)prop-2-en-1-one
0.000016
-
 pH and temperature not specified in the publication Staphylococcus aureus cis-3-4-dihydrohamacanthin B
0.000023
-
 pH and temperature not specified in the publication Staphylococcus aureus 2-(6-bromo-1,3-benzothiazol-2-yl)-1-(5-bromo-1H-indol-2-yl)ethan-1-one
0.000024
-
 pH and temperature not specified in the publication Staphylococcus aureus (2E)-3-(5-bromo-2-hydroxyphenyl)-1-(6-bromo-1H-indol-2-yl)prop-2-en-1-one
0.000043
-
 pH and temperature not specified in the publication Staphylococcus aureus 2-(6-bromo-1,3-benzothiazol-2-yl)-1-(3-bromo-2-hydroxyphenyl)ethan-1-one
0.000051
-
 pH and temperature not specified in the publication Staphylococcus aureus N-(5-bromo-1,3-benzothiazol-2-yl)-1H-indole-2-carboxamide
0.00006
-
 pH and temperature not specified in the publication Staphylococcus aureus bromodeoxytopsentin
0.000091
-
 pH and temperature not specified in the publication Staphylococcus aureus N'-[(1E)-1-(1H-benzimidazol-2-yl)ethylidene]-5-bromo-2-hydroxybenzohydrazide
0.000102
-
 pH and temperature not specified in the publication Staphylococcus aureus 6-bromo-3-(4-bromophenyl)-1H-indole
0.000116
-
 pH and temperature not specified in the publication Staphylococcus aureus 2-(3-bromo-2-hydroxyphenyl)-1-(6-bromo-1H-indol-2-yl)ethan-1-one
0.000126
-
 pH and temperature not specified in the publication Staphylococcus aureus N'-[(1E)-1-(1H-benzimidazol-2-yl)propylidene]-5-bromo-2-hydroxybenzohydrazide
0.000132
-
 pH and temperature not specified in the publication Staphylococcus aureus (2E)-1-(4-bromo-2-hydroxyphenyl)-3-(6-bromo-1H-indol-2-yl)prop-2-en-1-one
0.000214
-
 pH and temperature not specified in the publication Staphylococcus aureus 2-(6-bromo-1,3-benzothiazol-2-yl)-1-(4-bromo-2-hydroxyphenyl)ethan-1-one
0.000343
-
 pH and temperature not specified in the publication Staphylococcus aureus (2E)-3-(6-bromo-1H-indol-2-yl)-1-(2-hydroxyphenyl)prop-2-en-1-one
0.000355
-
 pH and temperature not specified in the publication Staphylococcus aureus (2E)-3-(5-bromo-2-hydroxyphenyl)-1-(1H-indol-2-yl)prop-2-en-1-one
0.000403
-
 pH and temperature not specified in the publication Staphylococcus aureus (2E)-3-(3-bromo-2-hydroxyphenyl)-1-(6-bromo-1H-indol-2-yl)prop-2-en-1-one
0.000553
-
 pH and temperature not specified in the publication Staphylococcus aureus (2E)-1-(4-bromo-2-hydroxyphenyl)-3-(1H-indol-2-yl)prop-2-en-1-one
0.00178
-
 pH and temperature not specified in the publication Staphylococcus aureus (2E)-3-(5-bromo-1H-indol-3-yl)-1-(1H-indol-2-yl)prop-2-en-1-one

General Information

General Information Comment Organism
physiological function pyruvate kinase (PK) is responsible for catalyzing the final step of glycolysis, which involves the transfer of the phosphoryl group of phosphoenolpyruvate (PEP) to ADP to produce pyruvate and ATP. Pyruvate kinase has been identified as a highly interconnected essential hub protein in methicillin-resistant Staphylococcus aureus (MRSA), with structural features distinct from the human homologues Staphylococcus aureus