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ID: ALA1165888

Journal: Eur J Med Chem

Title: Synthesis and study of antiproliferative activity of novel thienopyrimidines on glioblastoma cells.

Authors: Pédeboscq S, Gravier D, Casadebaig F, Hou G, Gissot A, De Giorgi F, Ichas F, Cambar J, Pometan JP.

Abstract: 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 receptor.

CiteXplore: 20219270

DOI: 10.1016/j.ejmech.2010.02.032