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BioAssay: AID 627981

Cytotoxicity against mouse RAW264.7 cells

We previously found that vitamin K(3) (menadione, 2-methyl-1,4-naphthoquinone) inhibits the activity of human mitochondrial DNA polymerase gamma (pol gamma). In this study, we focused on juglone (5-hydroxy-1,4-naphthoquinone), which is a 1,4-naphthoquinone derivative, and chemically synthesized novel juglones conjugated with C2:0 to C22:6 fatty acid (5-O-acyl juglones). The chemically modified more ..
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 Tested Compounds
 Tested Compounds
All(21)
 
 
Unspecified(21)
 
 
 Tested Substances
 Tested Substances
All(21)
 
 
Unspecified(21)
 
 
 Related BioAssays
 Related BioAssays
AID: 627981
Data Source: ChEMBL (785429)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2015-04-11

Data Table ( Complete ):           View All Data
Tested Compounds:
Description:
Title: Inhibitory effect of novel 5-O-acyl juglones on mammalian DNA polymerase activity, cancer cell growth and inflammatory response.

Abstract: We previously found that vitamin K(3) (menadione, 2-methyl-1,4-naphthoquinone) inhibits the activity of human mitochondrial DNA polymerase gamma (pol gamma). In this study, we focused on juglone (5-hydroxy-1,4-naphthoquinone), which is a 1,4-naphthoquinone derivative, and chemically synthesized novel juglones conjugated with C2:0 to C22:6 fatty acid (5-O-acyl juglones). The chemically modified juglones enhanced mammalian pol inhibition and their cytotoxic and anti-inflammatory activities. The juglone conjugated with oleic acid (C18:1-acyl juglone) showed the strongest inhibition of DNA replicative pol alpha activity and human colon carcinoma (HCT116) cell growth in 10 synthesized 5-O-acyl juglones. C12:0-Acyl juglone was the strongest inhibitor of DNA repair-related pol lambda, as well as the strongest suppression of the production of tumor necrosis factor (TNF)-alpha production induced by lipopolysaccharide (LPS) in the compounds tested. Moreover, this compound caused the greatest reduction in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute inflammation in mouse ears. C12:0- and C18:1-Acyl juglones selectively inhibited the activities of mammalian pol species, but did not influence the activities of other pols and DNA metabolic enzymes tested. These data indicate that the novel 5-O-acyl juglones target anti-cancer and/or anti-inflammatory agents based on mammalian pol inhibition. Moreover, the results suggest that acylation of juglone is an effective chemical modification to improve the anti-cancer and anti-inflammation of vitamin K(3) derivatives, such as juglone.
(PMID: 21903399)
Comment
Putative Target:
ChEMBL Target ID: 80418
Target Type: CELL-LINE
Cell Line: RAW264.7
Tissue: Monocytic-macrophage leukemia cells
Pref Name: RAW264.7
Organism: Mus musculus
Tax ID: 10090
Confidence: Target assigned is non-molecular
Relationship Type: Non-molecular target assigned
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: ADME
Assay Data Source: Scientific Literature
BAO: Assay Format: cell-based format
Assay Cell Type: RAW264.7
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1LD50*LD50 PubChem standard valueFloatμM
2LD50 activity commentLD50 activity commentString
3LD50 standard flagLD50 standard flagInteger
4LD50 qualifierLD50 qualifierString
5LD50 published valueLD50 published valueFloatμM
6LD50 standard valueLD50 standard valueFloatμM
7LD50 data validityLD50 data validityString

* Activity Concentration.

Data Table (Concise)
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