Abstract
Background: VEGFR-2 is a key regulator of cancer cell proliferation, migration and angiogenesis. Aim: Development of thieno[2,3-d]pyrimidine derivatives as potential anti-cancer agents targeting VEGFR-2. Methods: Seven in vitro and nine in silico studies were conducted. Results: Compound 10d demonstrated strong anticancer potential, boosting apoptosis based on VEGFR-2 inhibition. It arrested the S phase of the cell cycle and upregulated the apoptotic factors. Docking and molecular dynamics simulation studies confirm the stability of the VEGFR-2-10d complex and suggest that these compounds have good binding affinities to VEGFR-2. In addition, the drug-likeness was confirmed. Conclusion: Thieno[2,3-d]pyrimidines, particularly compound 10d, has good anticancer effects and may contribute to the development of new anticancer therapies.
Keywords:
MD simulations; VEGFR-2; apoptosis; docking; thieno[2,3-d]pyrimidine.
Publication types
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Research Support, Non-U.S. Gov't
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 Discovery*
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Drug Screening Assays, Antitumor
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Humans
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Molecular Docking Simulation
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Molecular Dynamics Simulation
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Molecular Structure
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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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Pyrimidines* / chemical synthesis
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Pyrimidines* / chemistry
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Pyrimidines* / 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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Pyrimidines
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Antineoplastic Agents
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Protein Kinase Inhibitors
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thieno(2,3-d)pyrimidine
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KDR protein, human