Abstract
Aim:
New pyrano[3,2-c]pyridine 4a-h, 5-8 and pyrano[2,3-d]pyrimidin 9a,b series were designed and chemically synthesized.
Methodology:
Using the standard drug doxorubicin, the novel chemical entities have been assessed in vitro as potential anticancer prospects on cell lines from liver, breast, colon, and lung cancer along with examining their inhibitory behaviors upon both EGFR and VEGFR-2 kinases.
Results & conclusion:
Compared to erlotinib (IC50 = 0.18 µM), compounds 8a and 8b demonstrated the highest anticancer activity with IC50 Values 0.23 and 0.15 µM, respectively). Further, derivative 8a illustrated encouraging inhibitory characteristics against EGFR and VEGFR-2 (IC50 = 1.21 and 2.65 μM, respectively). A computational study was used to estimate the physicochemical and pharmacokinetic properties to afford insightful information about the newly synthesized agents.
Keywords:
EGFR; Pyrano[3,2-c]pyridine; VEGFR-2; anti-cancer; apoptosis.
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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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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ErbB Receptors* / antagonists & inhibitors
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ErbB Receptors* / metabolism
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Humans
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Molecular Docking 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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Pyrans* / chemical synthesis
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Pyrans* / chemistry
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Pyrans* / pharmacology
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Pyridines* / chemical synthesis
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Pyridines* / chemistry
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Pyridines* / 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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Antineoplastic Agents
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Pyridines
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Vascular Endothelial Growth Factor Receptor-2
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Protein Kinase Inhibitors
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Pyrans
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ErbB Receptors
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EGFR protein, human
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KDR protein, human
Grants and funding
The authors extend their appreciation to Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2024R89), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia for funding this work.