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

被引:55
作者
Pedeboscq, Stephane [1 ,3 ]
Gravier, Denis [2 ]
Casadebaig, Francoise [2 ]
Hou, Genevieve [2 ]
Gissot, Arnaud [2 ]
De Giorgi, Francesca [3 ]
Ichas, Francois [3 ]
Cambard, Jean [4 ]
Pometan, Jean-Paul [1 ,2 ]
机构
[1] CHU Bordeaux, Hop St Andre, Serv Pharm, F-33075 Bordeaux, France
[2] Univ Victor Segalen Bordeaux 2, Chim Organ Lab, UFR Pharm, F-33076 Bordeaux, France
[3] Univ Victor Segalen Bordeaux 2, Inst Bergonie, INSERM, U916, F-33076 Bordeaux, France
[4] Univ Victor Segalen Bordeaux 2, Environm EA 3672, Lab Sante, Biol Cellulaire Lab, F-33076 Bordeaux, France
关键词
Thienopyrimidine; Epidermal growth factor receptor; Tyrosine kinase; Cytotoxicity; Apoptosis; TYROSINE KINASE INHIBITORS; GROWTH-FACTOR RECEPTOR; VIVO ANTICANCER ACTIVITY; BINDING-SITE INHIBITORS; IN-VITRO; POTENT; DERIVATIVES; DESIGN; AGENTS; UREAS;
D O I
10.1016/j.ejmech.2010.02.032
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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 mu M, 6b = 61.8 mu M, 6c = 41.2 mu M), suggesting a blockade of the EGFR pathway by binding to the TK receptor.
引用
收藏
页码:2473 / 2479
页数:7
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