Discovery of New 4-Alkoxyquinazoline-Based Derivatives as Potent VEGFR2 Inhibitors
| Autor: | Yan-Ting Wang, Hai-Liang Zhu, Peng-Cheng Lv, Fang Qiao, Xun Wu, She-Feng Wang, Yong Yin, Shao Sha |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
VEGF receptors
Angiogenesis Inhibitors Pharmacology Inhibitory postsynaptic potential Biochemistry Structure-Activity Relationship Cell Line Tumor Neoplasms Drug Discovery Ic50 values Humans Protein Kinase Inhibitors Cell Proliferation biology Cell growth Organic Chemistry Active site Kinase insert domain receptor respiratory system Vascular Endothelial Growth Factor Receptor-2 Molecular Docking Simulation Docking (molecular) Drug Design Quinazolines cardiovascular system biology.protein Molecular Medicine Tyrosine kinase circulatory and respiratory physiology |
| Zdroj: | Chemical Biology & Drug Design. 86:1323-1329 |
| ISSN: | 1747-0277 |
| DOI: | 10.1111/cbdd.12596 |
| Popis: | VEGFR2 has been proved to play a major role in the regulation of tumor angiogenesis. Twenty-one 4-alkoxyquinazoline-based derivatives have been designed and synthesized as vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors, and their biological activities were evaluated. Among these compounds, compound 3h exhibited the most potent inhibitory activities against VEGFR2 tyrosine kinase and cell proliferation, with the IC50 values of 2.89 nm (for VEGFR2) and 0.25 μm (for MCF-7), which were comparable with the control compound. Docking simulation was performed to position compound 3h into the 4ASE active site, and the result showed that compound 3h could bind well at the 4ASE active site. |
| Databáze: | OpenAIRE |
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