首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Synthesis,characterization and cytotoxicity studies of 1,2,3-triazoles and 1,2,4-triazolo [1,5-a] pyrimidines in human breast cancer cells
Authors:Maryam Gilandoust  Kachigere B Harsha  Chakrabhavi Dhananjaya Mohan  Ainiah Rushdiana Raquib  Shobith Rangappa  Vijay Pandey  Peter E Lobie  Kanchugarakoppal S Rangappa
Institution:1. Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysuru 570006, India;2. Department of Studies in Molecular Biology, University of Mysore, Manasagangotri, Mysuru 570006, India;3. Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore;4. Adichunchanagiri Institute for Molecular Medicine (AIMM), BG Nagara, Nagamangala Taluk, Mandya district 571448, India;5. Laboratory of Chemical Biology, Department of studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysuru 570006, India;6. Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, Guangdong 518005, PR China
Abstract:Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) is essential for physiological functions of tissues and neovasculature. VEGFR signaling is associated with the progression of pathological angiogenesis in various types of malignancies, making it an attractive therapeutic target in cancer treatment. In the present work, we report the synthesis of 1,4-disubstituted 1,2,3-triazoles and 1,2,4-triazolo1, 5-a]pyrimidine derivatives via copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction and screened for their anticancer activity against MCF7 cells. We identified 1-(2′-ethoxy-4′-fluoro-1,1′-biphenyl]-4-yl)-4-phenyl-1H-1,2,3-triazole (EFT) as lead cytotoxic agent against MCF7 cell lines with an IC50 value of 1.69?µM. Further evaluation revealed that EFT induces cytotoxicity on Ishikawa, MDA-MB-231 and BT474 cells with IC50 values of 1.97, 4.81 and 4.08?µM respectively. However, EFT did not induce cytotoxicity in normal lung epithelial (BEAS-2B) cells. Previous reports suggested that 1,2,3-triazoles are the inhibitors of VEGFR1 and therefore, we evaluated the effect of EFT on the expression of VEGFR1. The results demonstrated that EFT downregulates the expression of VEGFR1 in MCF7 cells. In summary, we identified a potent cytotoxic agent that imparts its antiproliferative activity by targeting VEGFR1 in breast cancer cells. The novel compound could serve as a lead structure in developing VEGFR1 inhibitors.
Keywords:EFT  1-(2′-ethoxy-4′-fluoro-[1  1′-biphenyl]-4-yl)-4-phenyl-1H-1  2  3-triazole  1  2  3-Triazole  1  2  4-Triazole  Angiogenesis  VEGFR1  Anticancer agent
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号