Abstract
Because both c-Src and iNOS are key regulatory enzymes in tumorigenesis, a new series of 4-heteroarylamino-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, prepared, and evaluated for blocking multiple signaling pathways 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 could inhibit both enzymes, and several of them showed potent inhibition activity against different cancer cell lines. The best compound 20 (CPU-Y020) showed the IC(50) values of 6.58 and 7.61microM toward colon cancer HT-29 and liver cancer HepG2 cell lines.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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CSK Tyrosine-Protein Kinase
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Cell Line, Tumor
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Drug Design*
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Growth Inhibitors / chemical synthesis
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Growth Inhibitors / pharmacology
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HT29 Cells
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Humans
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Nitric Oxide Synthase Type II / antagonists & inhibitors*
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Nitriles / chemical synthesis*
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Nitriles / pharmacology
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Protein Kinase Inhibitors / chemical synthesis*
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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 / pharmacology
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src-Family Kinases
Substances
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Growth Inhibitors
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Nitriles
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Protein Kinase Inhibitors
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Quinolines
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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