Design, synthesis and biological characteristics of pyrazolo[3,4-d]pyrimidine derivatives as potential VEGFR-2 inhibitors
| Autor: | Dan-Xia Ying, Ju Wang, Xiu-Fang Li, Wen Zhang, Guo-Wu Rao |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Future Medicinal Chemistry. 14:1649-1662 |
| ISSN: | 1756-8927 1756-8919 |
| DOI: | 10.4155/fmc-2022-0130 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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