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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)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2013-07-07

Data Table ( Complete ):           All
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
ChEMBL Assay Type: ADMET

ChEMBL Assay Data Source: Scientific Literature

ChEMBL 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

* Activity Concentration.

Data Table (Concise)
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