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

Stéphane Pédeboscq, Denis Gravier, Françoise Casadebaig, Geneviève Hou, Arnaud Gissot, Francesca De Giorgi, François Ichas, Jean Cambar, Jean-Paul Pometan
European Journal of Medicinal Chemistry. 2010-06-01; 45(6): 2473-2479
DOI: 10.1016/j.ejmech.2010.02.032

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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 microM, 6b=61.8 microM,
6c=41.2 microM), suggesting a blockade of the EGFR pathway by binding to the TK


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