Abstract
More than 50 new diaminoquinazoline derivatives have been synthesized and evaluated in a colon carcinoma cell growth inhibition assay using HCT116 and SW480 cells. Twenty compounds with good cell growth inhibitory activities (<4 μM) were tested as inhibitors of the β-catenin/T cell transcription factor 4 (Tcf4) signaling pathway using a HCT116 cell-based luciferase reporter assay. Results from the biological activities as well as the comparative molecular field analysis (CoMFA) of the properties of the molecules yielded a preliminary structure-activity relationship (SAR). Three potent compounds, 74, 78, and 86, showed IC(50) values <1 μM for growth inhibition of HCT116 cells and ∼1 μM for SW480 cells, as well as IC(50) values of 1.5-2.5 μM for HCT116 cells with the luciferase reporter assay.
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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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / physiology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Drug Design
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Drug Screening Assays, Antitumor
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Genes, Reporter
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Humans
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Luciferases / genetics
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Models, Molecular
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Quinazolines / chemical synthesis*
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Quinazolines / chemistry
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Quinazolines / pharmacology
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Signal Transduction
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Structure-Activity Relationship
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Transcription Factor 4
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Transcription Factors / physiology*
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beta Catenin / physiology*
Substances
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Antineoplastic Agents
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Quinazolines
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TCF4 protein, human
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Transcription Factor 4
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Transcription Factors
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beta Catenin
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Luciferases