Abstract
The synthesis and biological activities of four novel bispyridinium cyclophanes as choline kinase (ChoK) inhibitors are presented. Their synthetic methodology has been optimized according to dilution, temperature, and reaction time and provides pure bispyridinium cyclophanes in high yields very easily. One of these cyclophanes (6, 4,8-diaza-3(1,4),9(4,1)-dipyridina-1(1,4),6(1,3)-dibenzenacyclodecaphan-3(1),9(1)-bis(ilium) dibromide) has an IC(50(ChoK)) of 0.3 microM and is the most potent human ChoK inhibitor described to date.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Choline Kinase / antagonists & inhibitors*
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
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Heterocyclic Compounds, 4 or More Rings / chemistry
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Heterocyclic Compounds, 4 or More Rings / pharmacology
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Humans
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Pyridines / chemical synthesis*
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Pyridines / chemistry
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Pyridines / pharmacology
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Pyridinium Compounds / chemical synthesis*
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Pyridinium Compounds / chemistry
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Pyridinium Compounds / pharmacology
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Structure-Activity Relationship
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Tumor Cells, Cultured
Substances
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4,8-diaza-3(1,4),9(4,1)-dipyridina-1(1,4),6(1,3)-dibenzenacyclodecaphan-3(1),9(1)-bis(ilium)
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Antineoplastic Agents
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Enzyme Inhibitors
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Heterocyclic Compounds, 4 or More Rings
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Pyridines
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Pyridinium Compounds
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Choline Kinase