Design,synthesis and biological evaluation of pyrimidine-based derivatives as VEGFR-2 tyrosine kinase inhibitors |
| |
| Affiliation: | 1. Beijing Key Laboratory of Environmental and Viral Oncology, College of Life Science and Bio-engineering, Beijing University of Technology, Pingleyuan Street No. 100, Chaoyang District, Beijing 100124, China;2. Tong Yi Tang Pharmaceutical Co., Ltd., Sui''an Industrial Park of Zhangpu County, Fujian Province 363200, China;1. Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, Nanchang, Jiangxi 330013, China;2. College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, China;1. College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China;2. Beijing Dalitai Pharmaceutical Technology Co., Ltd, Beijing 100176, China;3. Guangzhou Institute of Biomedicine and Health, Chinese Academy of Science, Guangzhou 510530, China;1. School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China;2. Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;3. Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;4. Pharmacology and Safety Evaluation Key Laboratory of Tibetan Medicine in Qinghai Province, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, China;1. Department of Chemistry, University of Delhi, Delhi 110007, India;2. National Center for Natural Products Research, University of Mississippi, MS-38677, USA;3. Department of Biomolecular Sciences, University of Mississippi, MS-38677, USA;4. Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia;1. School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China;2. Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001, China;3. Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou 450001, China |
| |
| Abstract: | Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a crucial role in tumor angiogenesis, and inhibition of the VEGFR-2 signaling pathway has already become an attractive approach for cancer therapy. In this study, a novel pyrimidine-based derivative 7j was designed as lead compound, and three series of potent VEGFR-2 inhibitors were synthesized and biologically evaluated against A549 and HepG2 cell lines. Compounds 7d, 9s and 13n exhibited superior inhibitory activities against A549 cell with IC50 ranged from 9.19 to 13.17 μM and HepG2 cell with IC50 ranged from 11.94 to 18.21 μM compared to those of Pazopanib (IC50 = 21.18 and 36.66 μM). In addition, molecular docking study was performed to investigate the binding capacity and binding mode between target compounds and VEGFR-2. |
| |
| Keywords: | VEGFR-2 inhibitors Pyrimidine-based derivatives Molecular docking |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
