Synthesis and study of antiproliferative activity of novel thienopyrimidines on glioblastoma cells

The receptor tyrosine kinases (for example EGFR, PDGFR, VEGFR) are a transmembrane protein family which plays a crucial role in tumor growth, survival, metastasis dissemination and angiogenesis. During the past 10 years, many tyrosine kinase inhibitors (TKIs) have been approved for cancer treatment...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2010-06, Vol.45 (6), p.2473-2479
Main Authors: Pédeboscq, Stéphane, Gravier, Denis, Casadebaig, Françoise, Hou, Geneviève, Gissot, Arnaud, De Giorgi, Francesca, Ichas, François, Cambar, Jean, Pometan, Jean-Paul
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Biological and medical sciences
Cell Line, Tumor
Cell Proliferation - drug effects
Cytotoxicity
Epidermal growth factor receptor
Gene Expression Regulation, Neoplastic - drug effects
General aspects
Glioblastoma - genetics
Glioblastoma - pathology
Humans
Inhibitory Concentration 50
Medical sciences
Pharmacology. Drug treatments
Pyrimidines - chemical synthesis
Pyrimidines - chemistry
Pyrimidines - pharmacology
Receptor, Epidermal Growth Factor - metabolism
Thienopyrimidine
Tyrosine kinase
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Summary:The receptor tyrosine kinases (for example EGFR, PDGFR, VEGFR) are a transmembrane protein family which plays a crucial role in tumor growth, survival, metastasis dissemination and angiogenesis. During the past 10 years, many tyrosine kinase inhibitors (TKIs) have been approved for cancer treatment (imatinib, gefitinib, erlotinib, sunitinib, sorafenib). These compounds generally possess a pyrrolo- or pyrimido- pyrimidine scaffold or approaching molecular structure. We synthesized 10 thienopyrimidine compounds (including 5 newly synthesized) whose scaffold is very similar to the agents cited above. The cytotoxicity of these agents was evaluated using a MTT assay and a flow cytometry technique on glioblastoma cell lines. Two compounds showed a similar cytotoxicity to the standard anti-EGFR gefitinib (IC50: gefitinib = 51.9 μM, 6b = 61.8 μM, 6c = 41.2 μM), suggesting a blockade of the EGFR pathway by binding to the TK receptor. [Display omitted]
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2010.02.032