Affiliation:
1. College of Pharmaceutical Science, Zhejiang University of Technology & Institute of Drug Development & Chemical Biology, Zhejiang University of Technology, Hangzhou, 310014, China
Abstract
Aim: Several VEGFR-2 inhibitors with the structure of [3,4-d]pyrimidine and based on sorafenib were designed and synthesized. Materials & methods: Cytotoxic activity was evaluated by MTT, wound healing and clone formation assays. Cell cycle and apoptosis were analyzed by flow cytometry. Molecular simulation and western blot were also applied. Results: Among them, II-1 significantly inhibited tumor cellular activity (IC50 = 5.90 ± 0.05 μM on HepG2 cells) compared with sorafenib (IC50 = 9.05 ± 0.54 μM on HepG2 cells). Molecular docking demonstrated that II-1 and sorafenib have the same hydrogen binding. Finally, the protein expression of phosphorylated VEGFR-2 was substantially reduced after II-1 treatment. Conclusion: Compound II-1 can inhibit VEFGR-2 activation and is an effective antitumor agent in liver cancer cells.
Funder
Natural Science Foundation of Zhejiang Province
National Natural Science Foundation of China
The Science and Technology Program of Zhejiang Province
New-shoot Talents Program of Zhejiang Province under Grant
Subject
Drug Discovery,Pharmacology,Molecular Medicine
Cited by
2 articles.
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