Abstract
In this study, a series of curcumin derivatives containing 1,2,3-triazole were designed and synthesized, and their inhibitory activities against the proliferation of lung cancer cells were studied. Compound 5 k (3,4-dichlorobenzyltriazole methyl curcumin) had the best activity against A549 cells, with a half-maximal inhibitory concentration (IC50 ) of 2.27 μM, which was approximately 10 times higher than that of the lead curcumin and higher than that of gefitinib (IC50 =8.64 μM). Western blotting revealed that 5 k increased the phosphorylation levels of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Compound 5 k also promoted the expression of the inhibitor of nuclear factor-κB (IκBα) and decreased that of nuclear factor-κB (NF-κB), signal transducer and activator of transcription 3 (STAT3), and β-catenin. Therefore, 5 k suppresses A549 cell proliferation by activating the mitogen-activated protein kinases and suppressing NF-κB/STAT3 signaling pathways. So, 5 k can potentially be used for treating non-small cell lung cancer.
Keywords:
1,2,3-triazole; MAPK; curcumin; lung cancer; zebrafish.
© 2021 Wiley-VCH GmbH.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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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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Antioxidants / chemical synthesis
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Antioxidants / chemistry
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Antioxidants / pharmacology*
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Biphenyl Compounds / antagonists & inhibitors
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Cells, Cultured
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Curcumin / chemical synthesis
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Curcumin / chemistry
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Curcumin / pharmacology*
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Humans
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Lung Neoplasms / drug therapy*
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism
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Molecular Structure
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism
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Neoplasms, Experimental / drug therapy
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Neoplasms, Experimental / metabolism
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Neoplasms, Experimental / pathology
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Picrates / antagonists & inhibitors
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STAT3 Transcription Factor / antagonists & inhibitors
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STAT3 Transcription Factor / metabolism
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Structure-Activity Relationship
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Triazoles / chemical synthesis
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Triazoles / chemistry
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Triazoles / pharmacology*
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Zebrafish
Substances
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Antineoplastic Agents
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Antioxidants
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Biphenyl Compounds
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NF-kappa B
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Picrates
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STAT3 Transcription Factor
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STAT3 protein, human
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Triazoles
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1,1-diphenyl-2-picrylhydrazyl
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Mitogen-Activated Protein Kinases
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Curcumin