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Synthesis of coumaperine derivatives: Their NF-κB inhibitory effect, inhibition of cell migration and their cytotoxic activity
Muthuraman S, Gopinath P, Nithya P, Gopas J, Kumar R.S.
Published in Elsevier Masson SAS
2017
PMID: 27810594
Volume: 125
   
Pages: 1076 - 1087
Abstract
Coumaperine (an amide alkaloid, present in white piper) and its derivatives were synthesized and investigated for their cytotoxicity against L428 and A549 cells and their NF-κB inhibitory activity. It was found that the coumaperine derivatives CP-9 and CP-38 suppress NF-κB subunits p50 and p65 in nuclear fractions by western blot and by NF-κB luciferase reporter gene assay in a dose dependent manner. Confirmation of these results was obtained by confocal microscopy. CP-9, CP-32 and CP-38 also exhibited dose dependent cell cytotoxicity in a L428 cells expressing constitutively active NF-κB and in A549 cells, with an IC50 value of 43.25 μg/ml, 0.39 μg/ml and 16.85 μg/ml respectively against L428 cells and 57.15 μg/ml, 69.1 μg/ml and 63.2 μg/ml respectively against A549 cells. In addition, the coumaperine derivatives show remarkable inhibitory activity on the cancer cell migration assay against A549 lung adenocarcinoma cells at the concentrations of 5 μg/ml, 10 μg/ml, and 5 μg/ml of CP-9, CP-32 and CP-38 respectively. Aromatic substituents and number of olefinic double bond in coumaperine derivatives found to influence the inhibitory activity. In luciferase reporter gene assay, di-olefin conjugated coumaperine derivatives, CP-38, CP-32 and PIP exhibited higher inhibitory activity than their corresponding tri-olefin conjugated coumaperine derivatives, CP-102, CP-146 and PIP-155 respectively. CP-32 with a stronger electron donating group (-N(CH3)2) showed better inhibitory activity in luciferase reporter gene assay and in cell proliferation of L428 cells. Simple coumaperine derivative (CP-9, with no substituent) effectively inhibited A549 cells proliferation and migration than the other coumaperine derivatives. CP-9 and CP-38 diminish significantly the NF-κB subunits (p50 and p65) of L428 cells in nuclear fractions at the dosage of 10 μg/ml and 30 μg/ml respectively. Which clearly shows that CP-9 and CP-38 inactivate the NF-κB pathway in vitro. © 2016 Elsevier Masson SAS
About the journal
JournalData powered by TypesetEuropean Journal of Medicinal Chemistry
PublisherData powered by TypesetElsevier Masson SAS
ISSN02235234
Open AccessNo
Concepts (59)
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    Alkaloid
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    Amide
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    Antineoplastic agent
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    Benzaldehyde
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    COUMAPERINE DERIVATIVE
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    Immunoglobulin enhancer binding protein
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    PIPERIDINE
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    SORBIC ACID
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    TRANSCRIPTION FACTOR RELA
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    TRANSCRIPTION FACTOR RELB
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    Unclassified drug
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    ANTIINFLAMMATORY AGENT
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    COUMAPERINE
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    Piperidine derivative
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    A549 CELL LINE
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    Article
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    Carbon nuclear magnetic resonance
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    CELL MIGRATION ASSAY
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    Cell proliferation
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    Comparative study
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    Confocal microscopy
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    Controlled study
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    Drug cytotoxicity
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    Drug synthesis
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    Human
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    Human cell
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    IC50
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    IMMUNOCYTOCHEMISTRY
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    LUCIFERASE ASSAY
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    Mass fragmentography
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    Migration inhibition
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    Protein depletion
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    Protein expression
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    Protein localization
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    Proton nuclear magnetic resonance
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    Reaction analysis
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    Structure activity relation
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    Temperature sensitivity
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    Western blotting
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    XTT ASSAY
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    Antagonists and inhibitors
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    Black pepper
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    Cell motion
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    Cell survival
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    Chemistry
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    Drug effects
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    Immunology
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    Neoplasms
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    Signal transduction
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    Synthesis
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    Tumor cell line
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    Anti-inflammatory agents
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    Antineoplastic agents
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    Cell line, tumor
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    Cell movement
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    Humans
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    NF-KAPPA B
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    PIPER NIGRUM
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    Piperidines