Abstract
Background: Nicotinamide-based VEGFR-2 inhibitors have good contribution in drug discovery.Aim: Development of novel nicotinamides as VEGFR-2 inhibitors.Methods: different in vitro and in silico assays were conducted to evaluate the VEGFR-2 inhibition and cytotoxicity.Results: Compound 16c displayed strongest anti-VEGFR-2 potentiality and good anti-proliferative effects. Compound 16c enhanced apoptosis and caused cell cycle arrest in the Pre-G1 and S phases. Compound 16c boosted the level of the apoptotic caspase-3 and inhibited the level of TNF-α and IL-6 in tumor cells. Molecular docking and molecular dynamics (MD) simulations indicated the outstanding binding potential of compound 16c against VEGFR-2.Conclusion: Compound 16c is a good candidate for the creation of a novel antiangiogenic lead anticancer medication.
Keywords:
ADMET; MD simulation; VEGFR-2; apoptosis; docking; nicotinamide.
Plain language summary
[Box: see text].
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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Apoptosis* / drug effects
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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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Humans
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Immunologic Factors / chemical synthesis
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Immunologic Factors / chemistry
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Immunologic Factors / pharmacology
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Molecular Docking Simulation*
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Molecular Dynamics Simulation
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Molecular Structure
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Niacinamide* / analogs & derivatives
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Niacinamide* / chemical synthesis
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Niacinamide* / chemistry
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Niacinamide* / pharmacology
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Protein Kinase Inhibitors* / chemical synthesis
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Protein Kinase Inhibitors* / chemistry
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Protein Kinase Inhibitors* / pharmacology
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Structure-Activity Relationship
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Vascular Endothelial Growth Factor Receptor-2* / antagonists & inhibitors
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Vascular Endothelial Growth Factor Receptor-2* / metabolism
Substances
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Vascular Endothelial Growth Factor Receptor-2
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Niacinamide
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Protein Kinase Inhibitors
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KDR protein, human
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Antineoplastic Agents
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Immunologic Factors