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  Novel 4-amino bis-pyridinium and bis-quinolinium derivatives as choline kinase inhibitors with antiproliferative activity against the human breast cancer SKBR-3 cell line.

Gomez-Perez, V., McSorley, T., See Too, W. C., Konrad, M., & Campos, J. M. (2012). Novel 4-amino bis-pyridinium and bis-quinolinium derivatives as choline kinase inhibitors with antiproliferative activity against the human breast cancer SKBR-3 cell line. ChemMedChem, 7(4), 663-669. doi:10.1002/cmdc.201100505.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000F-9D9C-3 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-CA94-A
Genre: Journal Article

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1478273.pdf (Publisher version), 364KB
 
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Gomez-Perez, V., Author
McSorley, T.1, Author              
See Too, W. C.1, Author              
Konrad, M.1, Author              
Campos, J. M., Author
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1Research Group of Enzyme Biochemistry, MPI for biophysical chemistry, Max Planck Society, ou_578612              

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Free keywords: Antitumor agents; bis-pyridinium; bis-quinolinium; inhibitors; SKBR-3 cells
 Abstract: Choline kinase (ChoK) is the first enzyme in the CDP-choline pathway that synthesizes phosphatidylcholine, the major phospholipid in eukaryotic cell membranes. Human ChoK has three isoforms: ChoKa1, a2, and b. Specific inhibition of ChoKa has been reported to selectively kill tumor cells. In this study, ten new symmetrical bis-pyridinium and bis-quinolinium derivatives were synthesized and tested for their ability to inhibit human ChoKa2. These compounds have electron-releasing groups at position 4 of the pyridinium or quinolinium rings. 1,1’-[(Butane-1,3-diylbis(benzene-1,4-diylmethylene)]bis[4-(4- bromo-N-methylanilino)pyridinium)] dibromide and 1,1’-(biphenyl- 3,3’-diylmethylene)bis[7-chloro-4-(perhydroazepine-1- yl)quinolinium] dibromide were identified as highly potent ChoK inhibitors with IC50 values of 80 nm. Kinetic enzymatic assays indicated a mixed and predominantly competitive mechanism of inhibition for these compounds, which exhibited strong antiproliferative activity (EC50 1 mm) against the human breast cancer SKBR3 cell line.

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Language(s): eng - English
 Dates: 2012-01-252012-04
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1002/cmdc.201100505
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Title: ChemMedChem
Source Genre: Journal
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Pages: - Volume / Issue: 7 (4) Sequence Number: - Start / End Page: 663 - 669 Identifier: -