Abstract
Certain pyridazine containing compounds 2a-f, 3a, b, 4a, b, 5a, b, 6a and b were synthesized and characterized by spectroscopic means and elemental analysis. All the synthesized compounds were screened for their cytotoxic activity in vitro on colon cancer cell line (HCT-116) and breast cancer cell line (MCF-7). In addition, the antitumor activity of the synthesized compounds was tested in vivo against Ehrlich's ascites carcinoma (EAC) solid tumor grown in mice. The in vitro vascular endothelial growth factor receptor (VEGFR) enzyme inhibition assay was carried out for the most active compounds at a single dose of 10 µM. The obtained results revealed that compound 5b, which showed potent cytotoxic activity against HCT-116 also, exhibited the highest inhibition in the VEGFR kinase assay (92.2%).
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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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Drug Design*
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Drug Screening Assays, Antitumor
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Female
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HCT116 Cells
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Humans
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MCF-7 Cells
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Mice
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Models, Molecular
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Molecular Structure
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Neoplasms, Experimental / drug therapy
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Neoplasms, Experimental / pathology
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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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Pyridazines / chemical synthesis
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Pyridazines / chemistry
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Pyridazines / pharmacology*
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Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
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Receptors, Vascular Endothelial Growth Factor / metabolism
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Pyridazines
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pyridazine
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Receptors, Vascular Endothelial Growth Factor