Synthesis, anti-proliferative activity, and toxicity of C super(4)(C super(5)) substituted N,N'-bis(arylmethyl)imidazolium salts

The syntheses and characterization of C super(4) and C super(5) substituted N,N'-bis(arylmethyl)imidazolium salts with hydrophilic or lipophilic substituents on the imidazole ring are reported. A structure-activity relationship study revealed that the lipophilicity of groups at the C super(4) a...

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Bibliographic Details
Published in:Tetrahedron 2016-09, Vol.72 (38), p.5729-5743
Main Authors: Shelton, Kerri L, DeBord, Michael A, Wagers, Patrick O, Southerland, Marie R, Taraboletti, Alexandra, Robishaw, Nikki K, Jackson, Daniel P, Tosanovic, Radisa, Kofron, William G, Tessier, Claire A, Paruchuri, Sailaja, Shriver, Leah P, Panzner, Matthew J, Youngs, Wiley J
Format: Article
Language:English
Subjects:
Biocompatibility
Biotechnology
Cancer
Effectiveness
Lipophilicity
Lungs
Panels
Toxicity
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Summary:The syntheses and characterization of C super(4) and C super(5) substituted N,N'-bis(arylmethyl)imidazolium salts with hydrophilic or lipophilic substituents on the imidazole ring are reported. A structure-activity relationship study revealed that the lipophilicity of groups at the C super(4) and C super(5) positions plays a crucial role in modulating the efficacy against select non-small cell lung cancer cell lines tested. Compounds 11-17 were determined to be the most active against the panel of cell lines studied. Compounds 11 and 12 were examined by the National Cancer Institute's Developmental Therapeutic Program where they were tested against the NCI-60 human cancer cell line panel in a one-dose and five-dose assay. Compound 11 had high activity against the nine lung cancer lines tested while 12 had cytotoxic effects against 59 of the 60 cell lines. Compound 11 was also studied in a murine model to determine its in vivo toxicity.
ISSN:0040-4020