Abstract
We herein report the design and synthesis of furoquinoline based novel molecules (16-36) and their in vitro multiple targeted inhibitory potency against PI3K/Akt phosphorylation and mTOR using cell based and cell-free kinase assay. In particular, compound 23 in addition to PI3K-mTOR inhibitory potency, it has shown potent inhibition of hypoxia-induced accumulation of HIF-1alpha protein in U251-HRE cell line. The inhibitory activities of compound 23 were confirmed by Western blot analysis, using human non-small cell lung carcinoma H-460 cell line and glioblastoma U251 cell lines.
MeSH terms
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Blotting, Western
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Cell Line, Tumor
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Drug Design
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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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Furans / chemical synthesis
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Furans / chemistry
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Furans / pharmacology
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Molecular Structure
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors*
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Phosphorylation / drug effects
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Protein Kinases / drug effects*
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Protein Kinases / metabolism
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
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Proto-Oncogene Proteins c-akt / metabolism
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Quinolines / chemical synthesis
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Quinolines / chemistry
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Quinolines / pharmacology
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Signal Transduction / drug effects
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Stereoisomerism
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Structure-Activity Relationship
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TOR Serine-Threonine Kinases
Substances
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7-methoxy-4-(4-nitrophenylthio)furo(2,3-b)quinoline
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Enzyme Inhibitors
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Furans
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Hypoxia-Inducible Factor 1, alpha Subunit
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Phosphoinositide-3 Kinase Inhibitors
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Quinolines
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Protein Kinases
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MTOR protein, human
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases