title: Synthesis and study of antiproliferative activity of novel thienopyrimidines on glioblastoma cells.
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.
authors.affiliation: Service Pharmacie, Hôpital Saint-André, CHU de Bordeaux, INSERM U916, Institut Bergonié, Université Victor Segalen Bordeaux 2, 229 cours de l'Argonne, 33 076 Bordeaux, France. stephane.pedeboscq@chu-bordeaux.fr
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pédeboscq
authors.forename: Denis
authors.initials: D
authors.lastname: Gravier
authors.forename: Françoise
authors.initials: F
authors.lastname: Casadebaig
authors.forename: Geneviève
authors.initials: G
authors.lastname: Hou
authors.forename: Arnaud
authors.initials: A
authors.lastname: Gissot
authors.forename: Francesca
authors.initials: F
authors.lastname: De Giorgi
authors.forename: François
authors.initials: F
authors.lastname: Ichas
authors.forename: Jean
authors.initials: J
authors.lastname: Cambar
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Pometan
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D020128:Inhibitory Concentration 50; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; C476003:thienopyrimidine; D066246:ErbB Receptors