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BioAssay: AID 40629

Inhibition of autophosphorylation of the two-component signal transduction system kinase was measured using the KinA/Spo0F regulatory system of Bacillus subtilis.

A new class of inhibitors of the two-component regulatory systems (TCS) of bacteria was discovered based on the salicylanilide screening hits, closantel (1) and tetrachlorosalicylanilide (9). A systematic SAR study versus a model TCS, KinA/Spo0F, demonstrated the importance of electron-attracting substituents in the salicyloyl ring and hydrophobic groups in the anilide moiety for optimal more ..
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 Tested Compounds
 Tested Compounds
All(24)
 
 
Active(9)
 
 
Unspecified(15)
 
 
 Tested Substances
 Tested Substances
All(24)
 
 
Active(9)
 
 
Unspecified(15)
 
 
AID: 40629
Data Source: ChEMBL (37761)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-24
Modify Date: 2014-05-19

Data Table ( Complete ):           Active    All
Targets
Sequence: RecName: Full=Sporulation initiation phosphotransferase F; AltName: Full=Stage 0 sporulation protein F
Description ..   
Protein Family: REC
Comment ..   

Gene:SPO0F     Related Protein 3D Structures     More BioActivity Data..


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BioActive Compounds: 9
Description:
Title: Substituted salicylanilides as inhibitors of two-component regulatory systems in bacteria.

Abstract: A new class of inhibitors of the two-component regulatory systems (TCS) of bacteria was discovered based on the salicylanilide screening hits, closantel (1) and tetrachlorosalicylanilide (9). A systematic SAR study versus a model TCS, KinA/Spo0F, demonstrated the importance of electron-attracting substituents in the salicyloyl ring and hydrophobic groups in the anilide moiety for optimal activity. In addition, derivatives 8 and 16, containing the 2, 3-dihydroxybenzanilide structural motif, were potent inhibitors of the autophosphorylation of the KinA kinase, with IC50s of 2.8 and 6. 3 &microM, respectively. Compound 8 also inhibited the TCS mediating vancomycin resistance (VanS/VanR) in a genetically engineered Enterococcus faecalis cell line at concentrations subinhibitory for growth. Closantel (1), tetrachlorosalicylanilide (9), and several related derivatives (2, 7, 10, 11, 20) had antibacterial activity against the drug-resistant organisms, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF).
(PMID: 9685233)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
Assay Type: Functional

Assay Data Source: Scientific Literature

Target Type: Target is a group of closely related proteins

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2IC50 activity commentIC50 activity commentString
3IC50 standard flagIC50 standard flagInteger
4IC50 qualifierIC50 qualifierString
5IC50 published valueIC50 published valueFloatμM
6IC50 standard valueIC50 standard valueFloatnM
7IC50 data validityIC50 data validityString

* Activity Concentration.

Data Table (Concise)
Classification
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