Abstract
Because both c-Src and iNOS are key regulatory enzymes in tumorigenesis, a new series of 4-heterocycle amine-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, synthesized and evaluated as multiple targets agents in cancer therapy. All compounds were evaluated by two related enzyme inhibition assays and an anti-proliferation assay in vitro. The results showed that most compounds inhibited c-Src and iNOS well. The best compound 8 inhibited both enzymes with the IC(50) values of 34.8 nM and 26.7 microM. Several compounds also showed moderate anti-proliferation at 10 microM against colon and liver cancer cell lines.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aniline Compounds / chemical synthesis*
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Aniline Compounds / chemistry
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Aniline Compounds / pharmacology*
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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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CSK Tyrosine-Protein Kinase
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Drug Design*
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HT29 Cells
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Humans
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Molecular Structure
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Nitric Oxide Synthase Type II / antagonists & inhibitors*
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Nitriles / chemical synthesis*
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Nitriles / chemistry
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Nitriles / pharmacology*
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Quinolines / chemical synthesis*
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Quinolines / chemistry
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Quinolines / pharmacology*
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Structure-Activity Relationship
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src-Family Kinases
Substances
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Aniline Compounds
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Antineoplastic Agents
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Nitriles
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Protein Kinase Inhibitors
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Quinolines
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bosutinib
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Nitric Oxide Synthase Type II
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Protein-Tyrosine Kinases
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CSK Tyrosine-Protein Kinase
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src-Family Kinases
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CSK protein, human