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 (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.
Pédeboscq
Stéphane
S
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
Gravier
Denis
D
Casadebaig
Françoise
F
Hou
Geneviève
G
Gissot
Arnaud
A
De Giorgi
Francesca
F
Ichas
François
F
Cambar
Jean
J
Pometan
Jean-Paul
JP
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*
D000970:Antineoplastic Agents; D011743:Pyrimidines; C476003:thienopyrimidine; D066246:ErbB Receptors